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1. Synthesis and Antimicrobial Activity of Aminoalkyl Resveratrol Derivatives Inspired by Cationic Peptides

Author: Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica, Junta de Andalucía, Dutch Research Council (NWA). Paises Bajos, National Institute of Allergy and Infectious Diseases (NIAID). USA, Cebrián, Rubén, Lucas Rodríguez, Ricardo, Fernández Cantos, María Victoria, Slot, Koen, Peñalver, Pablo, Martínez García, Marta, Párraga Leo, Antonio, Paz Báñez, María Violante de, García, Federico, Kuipers, Oscar P., Morales, Juan Carlos, Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica, Junta de Andalucía, Dutch Research Council (NWA). Paises Bajos, National Institute of Allergy and Infectious Diseases (NIAID). USA, Cebrián, Rubén, Lucas Rodríguez, Ricardo, Fernández Cantos, María Victoria, Slot, Koen, Peñalver, Pablo, Martínez García, Marta, Párraga Leo, Antonio, Paz Báñez, María Violante de, García, Federico, Kuipers, Oscar P., and Morales, Juan Carlos
Abstract: Antimicrobial resistance is a global concern, far from being resolved. The need of new drugs against new targets is imminent. In this work, we present a family of aminoalkyl resveratrol derivatives with antibacterial activity inspired by the properties of cationic amphipathic antimicrobial peptides. Surprisingly, the newly designed molecules display modest activity against aerobically growing bacteria but show surprisingly good antimicrobial activity against anaerobic bacteria (Gram-negative and Gram-positive) suggesting specificity towards this bacterial group. Preliminary studies into the action mechanism suggest that activity takes place at the membrane level, while no cross-resistance with traditional antibiotics is observed. Actually, some good synergistic relations with existing antibiotics were found against Gram-negative pathogens. However, some cytotoxicity was observed, despite their low haemolytic activity. Our results show the importance of the balance between positively charged moieties and hydrophobicity to improve antimicrobial activity, setting the stage for the design of new drugs based on these molecules.
Published: 2023

2. Synthesis and Antimicrobial Activity of Aminoalkyl Resveratrol Derivatives Inspired by Cationic Peptides

Author: Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica, Junta de Andalucía, Dutch Research Council (NWA). Paises Bajos, National Institute of Allergy and Infectious Diseases (NIAID). USA, Cebrián, Rubén, Lucas Rodríguez, Ricardo, Fernández Cantos, María Victoria, Slot, Koen, Peñalver, Pablo, Martínez García, Marta, Párraga Leo, Antonio, Paz Báñez, María Violante de, García, Federico, Kuipers, Oscar P., Morales, Juan Carlos, Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica, Junta de Andalucía, Dutch Research Council (NWA). Paises Bajos, National Institute of Allergy and Infectious Diseases (NIAID). USA, Cebrián, Rubén, Lucas Rodríguez, Ricardo, Fernández Cantos, María Victoria, Slot, Koen, Peñalver, Pablo, Martínez García, Marta, Párraga Leo, Antonio, Paz Báñez, María Violante de, García, Federico, Kuipers, Oscar P., and Morales, Juan Carlos
Abstract: Antimicrobial resistance is a global concern, far from being resolved. The need of new drugs against new targets is imminent. In this work, we present a family of aminoalkyl resveratrol derivatives with antibacterial activity inspired by the properties of cationic amphipathic antimicrobial peptides. Surprisingly, the newly designed molecules display modest activity against aerobically growing bacteria but show surprisingly good antimicrobial activity against anaerobic bacteria (Gram-negative and Gram-positive) suggesting specificity towards this bacterial group. Preliminary studies into the action mechanism suggest that activity takes place at the membrane level, while no cross-resistance with traditional antibiotics is observed. Actually, some good synergistic relations with existing antibiotics were found against Gram-negative pathogens. However, some cytotoxicity was observed, despite their low haemolytic activity. Our results show the importance of the balance between positively charged moieties and hydrophobicity to improve antimicrobial activity, setting the stage for the design of new drugs based on these molecules.
Published: 2023

3. Synthesis and Antimicrobial Activity of Aminoalkyl Resveratrol Derivatives Inspired by Cationic Peptides

Author: Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica, Junta de Andalucía, Dutch Research Council (NWA). Paises Bajos, National Institute of Allergy and Infectious Diseases (NIAID). USA, Cebrián, Rubén, Lucas Rodríguez, Ricardo, Fernández Cantos, María Victoria, Slot, Koen, Peñalver, Pablo, Martínez García, Marta, Párraga Leo, Antonio, Paz Báñez, María Violante de, García, Federico, Kuipers, Oscar P., Morales, Juan Carlos, Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica, Junta de Andalucía, Dutch Research Council (NWA). Paises Bajos, National Institute of Allergy and Infectious Diseases (NIAID). USA, Cebrián, Rubén, Lucas Rodríguez, Ricardo, Fernández Cantos, María Victoria, Slot, Koen, Peñalver, Pablo, Martínez García, Marta, Párraga Leo, Antonio, Paz Báñez, María Violante de, García, Federico, Kuipers, Oscar P., and Morales, Juan Carlos
Abstract: Antimicrobial resistance is a global concern, far from being resolved. The need of new drugs against new targets is imminent. In this work, we present a family of aminoalkyl resveratrol derivatives with antibacterial activity inspired by the properties of cationic amphipathic antimicrobial peptides. Surprisingly, the newly designed molecules display modest activity against aerobically growing bacteria but show surprisingly good antimicrobial activity against anaerobic bacteria (Gram-negative and Gram-positive) suggesting specificity towards this bacterial group. Preliminary studies into the action mechanism suggest that activity takes place at the membrane level, while no cross-resistance with traditional antibiotics is observed. Actually, some good synergistic relations with existing antibiotics were found against Gram-negative pathogens. However, some cytotoxicity was observed, despite their low haemolytic activity. Our results show the importance of the balance between positively charged moieties and hydrophobicity to improve antimicrobial activity, setting the stage for the design of new drugs based on these molecules.
Published: 2023

4. Cesin, a short natural variant of nisin, displays potent antimicrobial activity against major pathogens despite lacking two C-terminal macrocycles

Author: Wang, Hui, Wang, H ( Hui ), Guo, Longcheng; https://orcid.org/0000-0003-4409-7935, Wambui, Joseph; https://orcid.org/0000-0002-6071-5505, Wang, Chenhui, Muchaamba, Francis; https://orcid.org/0000-0003-2266-3318, Fernandez-Cantos, Maria Victoria, Broos, Jaap, Tasara, Taurai; https://orcid.org/0000-0003-3377-8858, Kuipers, Oscar P; https://orcid.org/0000-0001-5596-7735, Stephan, Roger; https://orcid.org/0000-0003-1002-4762, Wang, Hui, Wang, H ( Hui ), Guo, Longcheng; https://orcid.org/0000-0003-4409-7935, Wambui, Joseph; https://orcid.org/0000-0002-6071-5505, Wang, Chenhui, Muchaamba, Francis; https://orcid.org/0000-0003-2266-3318, Fernandez-Cantos, Maria Victoria, Broos, Jaap, Tasara, Taurai; https://orcid.org/0000-0003-3377-8858, Kuipers, Oscar P; https://orcid.org/0000-0001-5596-7735, and Stephan, Roger; https://orcid.org/0000-0003-1002-4762
Abstract: Nisin is a widely used lantibiotic owing to its potent antimicrobial activity and its food-grade status. Its mode of action includes cell wall synthesis inhibition and pore formation, which are attributed to the lipid II binding and pore-forming domains, respectively. We discovered cesin, a short natural variant of nisin, produced by the psychrophilic anaerobe Clostridium estertheticum. Unlike other natural nisin variants, cesin lacks the two terminal macrocycles constituting the pore-forming domain. The current study aimed at heterologous expression and characterization of the antimicrobial activity and physicochemical properties of cesin. Following the successful heterologous expression of cesin in Lactococcus lactis, the lantibiotic demonstrated a broad and potent antimicrobial profile comparable to that of nisin. Determination of its mode of action using lipid II and lipoteichoic acid binding assays linked the potent antimicrobial activity to lipid II binding and electrostatic interactions with teichoic acids. Fluorescence microscopy showed that cesin lacks pore-forming ability in its natural form. Stability tests have shown the lantibiotic is highly stable at different pH values and temperature conditions, but that it can be degraded by trypsin. However, a bioengineered analog, cesin R15G, overcame the trypsin degradation, while keeping full antimicrobial activity. This study shows that cesin is a novel (small) nisin variant that efficiently kills target bacteria by inhibiting cell wall synthesis without pore formation. IMPORTANCE The current increase in antibiotic-resistant pathogens necessitates the discovery and application of novel antimicrobials. In this regard, we recently discovered cesin, which is a short natural variant of nisin produced by the psychrophilic Clostridium estertheticum. However, its suitability as an antimicrobial compound was in doubt due to its structural resemblance to nisin(1-22), a bioengineered short variant of nisin with low antim
Published: 2023

5. Trade-Offs Predicted by Metabolic Network Structure Give Rise to Evolutionary Specialization and Phenotypic Diversification

Author: Ekkers, David M., Tusso Gomez, Sergio, Moreno-Gamez, Stefany, Rillo, Marina C., Kuipers, Oscar P., van Doorn, G. Sander, Ekkers, David M., Tusso Gomez, Sergio, Moreno-Gamez, Stefany, Rillo, Marina C., Kuipers, Oscar P., and van Doorn, G. Sander
Abstract: Mitigating trade-offs between different resource-utilization functions is key to an organism's ecological and evolutionary success. These trade-offs often reflect metabolic constraints with a complex molecular underpinning; therefore, their consequences for evolutionary processes have remained elusive. Here, we investigate how metabolic architecture induces resource-utilization constraints and how these constraints, in turn, elicit evolutionary specialization and diversification. Guided by the metabolic network structure of the bacterium Lactococcus cremoris, we selected two carbon sources (fructose and galactose) with predicted coutilization constraints. By evolving L. cremoris on either fructose, galactose, or a mix of both sugars, we imposed selection favoring divergent metabolic specializations or coutilization of both resources, respectively. Phenotypic characterization revealed the evolution of either fructose or galactose specialists in the single-sugar treatments. In the mixed-sugar regime, we observed adaptive diversification: both specialists coexisted, and no generalist evolved. Divergence from the ancestral phenotype occurred at key pathway junctions in the central carbon metabolism. Fructose specialists evolved mutations in the fbp and pfk genes that appear to balance anabolic and catabolic carbon fluxes. Galactose specialists evolved increased expression of pgmA (the primary metabolic bottleneck of galactose metabolism) and silencing of ptnABCD (the main glucose transporter) and ldh (regulator/enzyme of downstream carbon metabolism). Overall, our study shows how metabolic network architecture and historical contingency serve to predict targets of selection and inform the functional interpretation of evolved mutations. The elucidation of the relationship between molecular constraints and phenotypic trade-offs contributes to an integrative understanding of evolutionary specialization and diversification.
Published: 2022
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6. Trade-Offs Predicted by Metabolic Network Structure Give Rise to Evolutionary Specialization and Phenotypic Diversification

Author: Ekkers, David M., Tusso Gomez, Sergio, Moreno-Gamez, Stefany, Rillo, Marina C., Kuipers, Oscar P., van Doorn, G. Sander, Ekkers, David M., Tusso Gomez, Sergio, Moreno-Gamez, Stefany, Rillo, Marina C., Kuipers, Oscar P., and van Doorn, G. Sander
Abstract: Mitigating trade-offs between different resource-utilization functions is key to an organism's ecological and evolutionary success. These trade-offs often reflect metabolic constraints with a complex molecular underpinning; therefore, their consequences for evolutionary processes have remained elusive. Here, we investigate how metabolic architecture induces resource-utilization constraints and how these constraints, in turn, elicit evolutionary specialization and diversification. Guided by the metabolic network structure of the bacterium Lactococcus cremoris, we selected two carbon sources (fructose and galactose) with predicted coutilization constraints. By evolving L. cremoris on either fructose, galactose, or a mix of both sugars, we imposed selection favoring divergent metabolic specializations or coutilization of both resources, respectively. Phenotypic characterization revealed the evolution of either fructose or galactose specialists in the single-sugar treatments. In the mixed-sugar regime, we observed adaptive diversification: both specialists coexisted, and no generalist evolved. Divergence from the ancestral phenotype occurred at key pathway junctions in the central carbon metabolism. Fructose specialists evolved mutations in the fbp and pfk genes that appear to balance anabolic and catabolic carbon fluxes. Galactose specialists evolved increased expression of pgmA (the primary metabolic bottleneck of galactose metabolism) and silencing of ptnABCD (the main glucose transporter) and ldh (regulator/enzyme of downstream carbon metabolism). Overall, our study shows how metabolic network architecture and historical contingency serve to predict targets of selection and inform the functional interpretation of evolved mutations. The elucidation of the relationship between molecular constraints and phenotypic trade-offs contributes to an integrative understanding of evolutionary specialization and diversification.
Published: 2022
Full Text: View/download PDF

7. Trade-Offs Predicted by Metabolic Network Structure Give Rise to Evolutionary Specialization and Phenotypic Diversification

Author: Ekkers, David M., Tusso Gomez, Sergio, Moreno-Gamez, Stefany, Rillo, Marina C., Kuipers, Oscar P., van Doorn, G. Sander, Ekkers, David M., Tusso Gomez, Sergio, Moreno-Gamez, Stefany, Rillo, Marina C., Kuipers, Oscar P., and van Doorn, G. Sander
Abstract: Mitigating trade-offs between different resource-utilization functions is key to an organism's ecological and evolutionary success. These trade-offs often reflect metabolic constraints with a complex molecular underpinning; therefore, their consequences for evolutionary processes have remained elusive. Here, we investigate how metabolic architecture induces resource-utilization constraints and how these constraints, in turn, elicit evolutionary specialization and diversification. Guided by the metabolic network structure of the bacterium Lactococcus cremoris, we selected two carbon sources (fructose and galactose) with predicted coutilization constraints. By evolving L. cremoris on either fructose, galactose, or a mix of both sugars, we imposed selection favoring divergent metabolic specializations or coutilization of both resources, respectively. Phenotypic characterization revealed the evolution of either fructose or galactose specialists in the single-sugar treatments. In the mixed-sugar regime, we observed adaptive diversification: both specialists coexisted, and no generalist evolved. Divergence from the ancestral phenotype occurred at key pathway junctions in the central carbon metabolism. Fructose specialists evolved mutations in the fbp and pfk genes that appear to balance anabolic and catabolic carbon fluxes. Galactose specialists evolved increased expression of pgmA (the primary metabolic bottleneck of galactose metabolism) and silencing of ptnABCD (the main glucose transporter) and ldh (regulator/enzyme of downstream carbon metabolism). Overall, our study shows how metabolic network architecture and historical contingency serve to predict targets of selection and inform the functional interpretation of evolved mutations. The elucidation of the relationship between molecular constraints and phenotypic trade-offs contributes to an integrative understanding of evolutionary specialization and diversification.
Published: 2022
Full Text: View/download PDF

8. Trade-Offs Predicted by Metabolic Network Structure Give Rise to Evolutionary Specialization and Phenotypic Diversification

Author: Ekkers, David M., Tusso Gomez, Sergio, Moreno-Gamez, Stefany, Rillo, Marina C., Kuipers, Oscar P., van Doorn, G. Sander, Ekkers, David M., Tusso Gomez, Sergio, Moreno-Gamez, Stefany, Rillo, Marina C., Kuipers, Oscar P., and van Doorn, G. Sander
Abstract: Mitigating trade-offs between different resource-utilization functions is key to an organism's ecological and evolutionary success. These trade-offs often reflect metabolic constraints with a complex molecular underpinning; therefore, their consequences for evolutionary processes have remained elusive. Here, we investigate how metabolic architecture induces resource-utilization constraints and how these constraints, in turn, elicit evolutionary specialization and diversification. Guided by the metabolic network structure of the bacterium Lactococcus cremoris, we selected two carbon sources (fructose and galactose) with predicted coutilization constraints. By evolving L. cremoris on either fructose, galactose, or a mix of both sugars, we imposed selection favoring divergent metabolic specializations or coutilization of both resources, respectively. Phenotypic characterization revealed the evolution of either fructose or galactose specialists in the single-sugar treatments. In the mixed-sugar regime, we observed adaptive diversification: both specialists coexisted, and no generalist evolved. Divergence from the ancestral phenotype occurred at key pathway junctions in the central carbon metabolism. Fructose specialists evolved mutations in the fbp and pfk genes that appear to balance anabolic and catabolic carbon fluxes. Galactose specialists evolved increased expression of pgmA (the primary metabolic bottleneck of galactose metabolism) and silencing of ptnABCD (the main glucose transporter) and ldh (regulator/enzyme of downstream carbon metabolism). Overall, our study shows how metabolic network architecture and historical contingency serve to predict targets of selection and inform the functional interpretation of evolved mutations. The elucidation of the relationship between molecular constraints and phenotypic trade-offs contributes to an integrative understanding of evolutionary specialization and diversification.
Published: 2022
Full Text: View/download PDF

9. Trade-Offs Predicted by Metabolic Network Structure Give Rise to Evolutionary Specialization and Phenotypic Diversification

Author: Ekkers, David M., Tusso Gomez, Sergio, Moreno-Gamez, Stefany, Rillo, Marina C., Kuipers, Oscar P., van Doorn, G. Sander, Ekkers, David M., Tusso Gomez, Sergio, Moreno-Gamez, Stefany, Rillo, Marina C., Kuipers, Oscar P., and van Doorn, G. Sander
Abstract: Mitigating trade-offs between different resource-utilization functions is key to an organism's ecological and evolutionary success. These trade-offs often reflect metabolic constraints with a complex molecular underpinning; therefore, their consequences for evolutionary processes have remained elusive. Here, we investigate how metabolic architecture induces resource-utilization constraints and how these constraints, in turn, elicit evolutionary specialization and diversification. Guided by the metabolic network structure of the bacterium Lactococcus cremoris, we selected two carbon sources (fructose and galactose) with predicted coutilization constraints. By evolving L. cremoris on either fructose, galactose, or a mix of both sugars, we imposed selection favoring divergent metabolic specializations or coutilization of both resources, respectively. Phenotypic characterization revealed the evolution of either fructose or galactose specialists in the single-sugar treatments. In the mixed-sugar regime, we observed adaptive diversification: both specialists coexisted, and no generalist evolved. Divergence from the ancestral phenotype occurred at key pathway junctions in the central carbon metabolism. Fructose specialists evolved mutations in the fbp and pfk genes that appear to balance anabolic and catabolic carbon fluxes. Galactose specialists evolved increased expression of pgmA (the primary metabolic bottleneck of galactose metabolism) and silencing of ptnABCD (the main glucose transporter) and ldh (regulator/enzyme of downstream carbon metabolism). Overall, our study shows how metabolic network architecture and historical contingency serve to predict targets of selection and inform the functional interpretation of evolved mutations. The elucidation of the relationship between molecular constraints and phenotypic trade-offs contributes to an integrative understanding of evolutionary specialization and diversification.
Published: 2022
Full Text: View/download PDF

10. Brevibacillin 2V Exerts Its Bactericidal Activity via Binding to Lipid II and Permeabilizing Cellular Membranes

Author: Sub Membrane Biochemistry & Biophysics, Sub NMR Spectroscopy, NMR Spectroscopy, Membrane Biochemistry and Biophysics, Zhao, Xinghong, Wang, Xiaoqi, Shukla, Rhythm, Kumar, Raj, Weingarth, Markus, Breukink, Eefjan, Kuipers, Oscar P, Sub Membrane Biochemistry & Biophysics, Sub NMR Spectroscopy, NMR Spectroscopy, Membrane Biochemistry and Biophysics, Zhao, Xinghong, Wang, Xiaoqi, Shukla, Rhythm, Kumar, Raj, Weingarth, Markus, Breukink, Eefjan, and Kuipers, Oscar P
Published: 2021

11. Brevibacillin 2V, a Novel Antimicrobial Lipopeptide With an Exceptionally Low Hemolytic Activity

Author: Sub Membrane Biochemistry & Biophysics, Sub NMR Spectroscopy, Membrane Biochemistry and Biophysics, NMR Spectroscopy, Zhao, Xinghong, Wang, Xiaoqi, Shukla, Rhythm, Kumar, Raj, Weingarth, Markus, Breukink, Eefjan, Kuipers, Oscar P, Sub Membrane Biochemistry & Biophysics, Sub NMR Spectroscopy, Membrane Biochemistry and Biophysics, NMR Spectroscopy, Zhao, Xinghong, Wang, Xiaoqi, Shukla, Rhythm, Kumar, Raj, Weingarth, Markus, Breukink, Eefjan, and Kuipers, Oscar P
Published: 2021

12. Brevibacillin 2V Exerts Its Bactericidal Activity via Binding to Lipid II and Permeabilizing Cellular Membranes

Author: Sub Membrane Biochemistry & Biophysics, Sub NMR Spectroscopy, NMR Spectroscopy, Membrane Biochemistry and Biophysics, Zhao, Xinghong, Wang, Xiaoqi, Shukla, Rhythm, Kumar, Raj, Weingarth, Markus, Breukink, Eefjan, Kuipers, Oscar P, Sub Membrane Biochemistry & Biophysics, Sub NMR Spectroscopy, NMR Spectroscopy, Membrane Biochemistry and Biophysics, Zhao, Xinghong, Wang, Xiaoqi, Shukla, Rhythm, Kumar, Raj, Weingarth, Markus, Breukink, Eefjan, and Kuipers, Oscar P
Published: 2021

13. Brevibacillin 2V, a Novel Antimicrobial Lipopeptide With an Exceptionally Low Hemolytic Activity

Author: Sub Membrane Biochemistry & Biophysics, Sub NMR Spectroscopy, Membrane Biochemistry and Biophysics, NMR Spectroscopy, Zhao, Xinghong, Wang, Xiaoqi, Shukla, Rhythm, Kumar, Raj, Weingarth, Markus, Breukink, Eefjan, Kuipers, Oscar P, Sub Membrane Biochemistry & Biophysics, Sub NMR Spectroscopy, Membrane Biochemistry and Biophysics, NMR Spectroscopy, Zhao, Xinghong, Wang, Xiaoqi, Shukla, Rhythm, Kumar, Raj, Weingarth, Markus, Breukink, Eefjan, and Kuipers, Oscar P
Published: 2021

14. Brevibacillin 2V Exerts Its Bactericidal Activity via Binding to Lipid II and Permeabilizing Cellular Membranes

Author: Sub Membrane Biochemistry & Biophysics, Sub NMR Spectroscopy, NMR Spectroscopy, Membrane Biochemistry and Biophysics, Zhao, Xinghong, Wang, Xiaoqi, Shukla, Rhythm, Kumar, Raj, Weingarth, Markus, Breukink, Eefjan, Kuipers, Oscar P, Sub Membrane Biochemistry & Biophysics, Sub NMR Spectroscopy, NMR Spectroscopy, Membrane Biochemistry and Biophysics, Zhao, Xinghong, Wang, Xiaoqi, Shukla, Rhythm, Kumar, Raj, Weingarth, Markus, Breukink, Eefjan, and Kuipers, Oscar P
Published: 2021

15. Brevibacillin 2V, a Novel Antimicrobial Lipopeptide With an Exceptionally Low Hemolytic Activity

Author: Sub Membrane Biochemistry & Biophysics, Sub NMR Spectroscopy, Membrane Biochemistry and Biophysics, NMR Spectroscopy, Zhao, Xinghong, Wang, Xiaoqi, Shukla, Rhythm, Kumar, Raj, Weingarth, Markus, Breukink, Eefjan, Kuipers, Oscar P, Sub Membrane Biochemistry & Biophysics, Sub NMR Spectroscopy, Membrane Biochemistry and Biophysics, NMR Spectroscopy, Zhao, Xinghong, Wang, Xiaoqi, Shukla, Rhythm, Kumar, Raj, Weingarth, Markus, Breukink, Eefjan, and Kuipers, Oscar P
Published: 2021

16. An Engineered Double Lipid II Binding Motifs-Containing Lantibiotic Displays Potent and Selective Antimicrobial Activity against Enterococcus faecium

Author: Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Zhao, Xinghong, Yin, Zhongqiong, Breukink, Eefjan, Moll, Gert N, Kuipers, Oscar P, Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Zhao, Xinghong, Yin, Zhongqiong, Breukink, Eefjan, Moll, Gert N, and Kuipers, Oscar P
Published: 2020

17. Microbial competition reduces metabolic interaction distances to the low µm-range

Author: van Tatenhove-Pel, R.J. (author), Rijavec, Tomaž (author), Lapanje, Aleš (author), van Swam, Iris (author), Zwering, Emile (author), Hernandez-Valdes, Jhonatan A. (author), Kuipers, Oscar P. (author), Picioreanu, C. (author), Teusink, Bas (author), Bachmann, Herwig (author), van Tatenhove-Pel, R.J. (author), Rijavec, Tomaž (author), Lapanje, Aleš (author), van Swam, Iris (author), Zwering, Emile (author), Hernandez-Valdes, Jhonatan A. (author), Kuipers, Oscar P. (author), Picioreanu, C. (author), Teusink, Bas (author), and Bachmann, Herwig (author)
Abstract: Metabolic interactions between cells affect microbial community compositions and hence their function in ecosystems. It is well-known that under competition for the exchanged metabolite, concentration gradients constrain the distances over which interactions can occur. However, interaction distances are typically quantified in two-dimensional systems or without accounting for competition or other metabolite-removal, conditions which may not very often match natural ecosystems. We here analyze the impact of cell-to-cell distance on unidirectional cross-feeding in a three-dimensional aqueous system with competition for the exchanged metabolite. Effective interaction distances were computed with a reaction-diffusion model and experimentally verified by growing a synthetic consortium of 1 µm-sized metabolite producer, receiver, and competitor cells in different spatial structures. We show that receivers cannot interact with producers located on average 15 µm away from them, as product concentration gradients flatten close to producer cells. We developed an aggregation protocol and varied the receiver cells’ product affinity, to show that within producer–receiver aggregates even low-affinity receiver cells could interact with producers. These results show that competition or other metabolite-removal of a public good in a three-dimensional system reduces metabolic interaction distances to the low µm-range, highlighting the importance of concentration gradients as physical constraint for cellular interactions., BT/Environmental Biotechnology
Published: 2020
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18. An Engineered Double Lipid II Binding Motifs-Containing Lantibiotic Displays Potent and Selective Antimicrobial Activity against Enterococcus faecium

Author: Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Zhao, Xinghong, Yin, Zhongqiong, Breukink, Eefjan, Moll, Gert N, Kuipers, Oscar P, Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Zhao, Xinghong, Yin, Zhongqiong, Breukink, Eefjan, Moll, Gert N, and Kuipers, Oscar P
Published: 2020

19. An Engineered Double Lipid II Binding Motifs-Containing Lantibiotic Displays Potent and Selective Antimicrobial Activity against Enterococcus faecium

Author: Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Zhao, Xinghong, Yin, Zhongqiong, Breukink, Eefjan, Moll, Gert N, Kuipers, Oscar P, Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Zhao, Xinghong, Yin, Zhongqiong, Breukink, Eefjan, Moll, Gert N, and Kuipers, Oscar P
Published: 2020

20. Microbial competition reduces metabolic interaction distances to the low µm-range

Author: van Tatenhove-Pel, R.J. (author), Rijavec, Tomaž (author), Lapanje, Aleš (author), van Swam, Iris (author), Zwering, Emile (author), Hernandez-Valdes, Jhonatan A. (author), Kuipers, Oscar P. (author), Picioreanu, C. (author), Teusink, Bas (author), Bachmann, Herwig (author), van Tatenhove-Pel, R.J. (author), Rijavec, Tomaž (author), Lapanje, Aleš (author), van Swam, Iris (author), Zwering, Emile (author), Hernandez-Valdes, Jhonatan A. (author), Kuipers, Oscar P. (author), Picioreanu, C. (author), Teusink, Bas (author), and Bachmann, Herwig (author)
Abstract: Metabolic interactions between cells affect microbial community compositions and hence their function in ecosystems. It is well-known that under competition for the exchanged metabolite, concentration gradients constrain the distances over which interactions can occur. However, interaction distances are typically quantified in two-dimensional systems or without accounting for competition or other metabolite-removal, conditions which may not very often match natural ecosystems. We here analyze the impact of cell-to-cell distance on unidirectional cross-feeding in a three-dimensional aqueous system with competition for the exchanged metabolite. Effective interaction distances were computed with a reaction-diffusion model and experimentally verified by growing a synthetic consortium of 1 µm-sized metabolite producer, receiver, and competitor cells in different spatial structures. We show that receivers cannot interact with producers located on average 15 µm away from them, as product concentration gradients flatten close to producer cells. We developed an aggregation protocol and varied the receiver cells’ product affinity, to show that within producer–receiver aggregates even low-affinity receiver cells could interact with producers. These results show that competition or other metabolite-removal of a public good in a three-dimensional system reduces metabolic interaction distances to the low µm-range, highlighting the importance of concentration gradients as physical constraint for cellular interactions., BT/Environmental Biotechnology
Published: 2020
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21. A riboswitch gives rise to multi-generational phenotypic heterogeneity in an auxotrophic bacterium

Author: Hernandez-Valdes, Jhonatan A; https://orcid.org/0000-0001-9186-4792, van Gestel, Jordi; https://orcid.org/0000-0001-5598-5239, Kuipers, Oscar P; https://orcid.org/0000-0001-5596-7735, Hernandez-Valdes, Jhonatan A; https://orcid.org/0000-0001-9186-4792, van Gestel, Jordi; https://orcid.org/0000-0001-5598-5239, and Kuipers, Oscar P; https://orcid.org/0000-0001-5596-7735
Abstract: Auxotrophy, the inability to produce an organic compound essential for growth, is widespread among bacteria. Auxotrophic bacteria rely on transporters to acquire these compounds from their environment. Here, we study the expression of both low- and high-affinity transporters of the costly amino acid methionine in an auxotrophic lactic acid bacterium, Lactococcus lactis. We show that the high-affinity transporter (Met-transporter) is heterogeneously expressed at low methionine concentrations, resulting in two isogenic subpopulations that sequester methionine in different ways: one subpopulation primarily relies on the high-affinity transporter (high expression of the Met-transporter) and the other subpopulation primarily relies on the low-affinity transporter (low expression of the Met-transporter). The phenotypic heterogeneity is remarkably stable, inherited for tens of generations, and apparent at the colony level. This heterogeneity results from a T-box riboswitch in the promoter region of the met operon encoding the high-affinity Met-transporter. We hypothesize that T-box riboswitches, which are commonly found in the Lactobacillales, may play as-yet unexplored roles in the predominantly auxotrophic lifestyle of these bacteria.
Published: 2020

22. BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits

Author: Dudnik, Alexey, Almeida, A. Filipa, Andrade, Ricardo, Avila, Barbara, Bañados, Pilar, Barbay, Diane, Bassard, Jean Etienne, Benkoulouche, Mounir, Bott, Michael, Braga, Adelaide, Breitel, Dario, Brennan, Rex, Bulteau, Laurent, Chanforan, Celine, Costa, Inês, Costa, Rafael S., Doostmohammadi, Mahdi, Faria, Nuno, Feng, Chengyong, Fernandes, Armando, Ferreira, Patricia, Ferro, Roberto, Foito, Alexandre, Freitag, Sabine, Garcia, Gonçalo, Gaspar, Paula, Godinho-Pereira, Joana, Hamberger, Björn, Hartmann, András, Heider, Harald, Jardim, Carolina, Julien-Laferriere, Alice, Kallscheuer, Nicolai, Kerbe, Wolfgang, Kuipers, Oscar P., Li, Shanshan, Love, Nicola, Marchetti-Spaccamela, Alberto, Marienhagen, Jan, Martin, Cathie, Mary, Arnaud, Mazurek, Vincent, Meinhart, Camillo, Sevillano, David Méndez, Menezes, Regina, Naesby, Michael, Nørholm, Morten H.H., Okkels, Finn T., Oliveira, Joana, Ottens, Marcel, Parrot, Delphine, Pei, Lei, Rocha, Isabel, Rosado-Ramos, Rita, Rousseau, Caroline, Sagot, Marie France, dos Santos, Claudia Nunes, Schmidt, Markus, Shelenga, Tatiana, Shepherd, Louise, Silva, Ana Rita, da Silva, Marcelo Henriques, Simon, Olivier, Stahlhut, Steen Gustav, Solopova, Ana, Sorokin, Artem, Stewart, Derek, Stougie, Leen, Su, Shang, Thole, Vera, Tikhonova, Olga, Trick, Martin, Vain, Philippe, Veríssimo, André, Vila-Santa, Ana, Vinga, Susana, Vogt, Michael, Wang, Liangsheng, Wang, Lijin, Wei, Wei, Youssef, Sandra, Neves, Ana Rute, Forster, Jochen, Dudnik, Alexey, Almeida, A. Filipa, Andrade, Ricardo, Avila, Barbara, Bañados, Pilar, Barbay, Diane, Bassard, Jean Etienne, Benkoulouche, Mounir, Bott, Michael, Braga, Adelaide, Breitel, Dario, Brennan, Rex, Bulteau, Laurent, Chanforan, Celine, Costa, Inês, Costa, Rafael S., Doostmohammadi, Mahdi, Faria, Nuno, Feng, Chengyong, Fernandes, Armando, Ferreira, Patricia, Ferro, Roberto, Foito, Alexandre, Freitag, Sabine, Garcia, Gonçalo, Gaspar, Paula, Godinho-Pereira, Joana, Hamberger, Björn, Hartmann, András, Heider, Harald, Jardim, Carolina, Julien-Laferriere, Alice, Kallscheuer, Nicolai, Kerbe, Wolfgang, Kuipers, Oscar P., Li, Shanshan, Love, Nicola, Marchetti-Spaccamela, Alberto, Marienhagen, Jan, Martin, Cathie, Mary, Arnaud, Mazurek, Vincent, Meinhart, Camillo, Sevillano, David Méndez, Menezes, Regina, Naesby, Michael, Nørholm, Morten H.H., Okkels, Finn T., Oliveira, Joana, Ottens, Marcel, Parrot, Delphine, Pei, Lei, Rocha, Isabel, Rosado-Ramos, Rita, Rousseau, Caroline, Sagot, Marie France, dos Santos, Claudia Nunes, Schmidt, Markus, Shelenga, Tatiana, Shepherd, Louise, Silva, Ana Rita, da Silva, Marcelo Henriques, Simon, Olivier, Stahlhut, Steen Gustav, Solopova, Ana, Sorokin, Artem, Stewart, Derek, Stougie, Leen, Su, Shang, Thole, Vera, Tikhonova, Olga, Trick, Martin, Vain, Philippe, Veríssimo, André, Vila-Santa, Ana, Vinga, Susana, Vogt, Michael, Wang, Liangsheng, Wang, Lijin, Wei, Wei, Youssef, Sandra, Neves, Ana Rute, and Forster, Jochen
Abstract: BACterial Hosts for production of Bioactive phenolics from bERRY fruits (BacHBerry) was a 3-year project funded by the Seventh Framework Programme (FP7) of the European Union that ran between November 2013 and October 2016. The overall aim of the project was to establish a sustainable and economically-feasible strategy for the production of novel high-value phenolic compounds isolated from berry fruits using bacterial platforms. The project aimed at covering all stages of the discovery and pre-commercialization process, including berry collection, screening and characterization of their bioactive components, identification and functional characterization of the corresponding biosynthetic pathways, and construction of Gram-positive bacterial cell factories producing phenolic compounds. Further activities included optimization of polyphenol extraction methods from bacterial cultures, scale-up of production by fermentation up to pilot scale, as well as societal and economic analyses of the processes. This review article summarizes some of the key findings obtained throughout the duration of the project.
Published: 2018
Full Text: View/download PDF

23. BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits

Author: Dudnik, Alexey, Almeida, A. Filipa, Andrade, Ricardo, Avila, Barbara, Bañados, Pilar, Barbay, Diane, Bassard, Jean Etienne, Benkoulouche, Mounir, Bott, Michael, Braga, Adelaide, Breitel, Dario, Brennan, Rex, Bulteau, Laurent, Chanforan, Celine, Costa, Inês, Costa, Rafael S., Doostmohammadi, Mahdi, Faria, Nuno, Feng, Chengyong, Fernandes, Armando, Ferreira, Patricia, Ferro, Roberto, Foito, Alexandre, Freitag, Sabine, Garcia, Gonçalo, Gaspar, Paula, Godinho-Pereira, Joana, Hamberger, Björn, Hartmann, András, Heider, Harald, Jardim, Carolina, Julien-Laferriere, Alice, Kallscheuer, Nicolai, Kerbe, Wolfgang, Kuipers, Oscar P., Li, Shanshan, Love, Nicola, Marchetti-Spaccamela, Alberto, Marienhagen, Jan, Martin, Cathie, Mary, Arnaud, Mazurek, Vincent, Meinhart, Camillo, Sevillano, David Méndez, Menezes, Regina, Naesby, Michael, Nørholm, Morten H.H., Okkels, Finn T., Oliveira, Joana, Ottens, Marcel, Parrot, Delphine, Pei, Lei, Rocha, Isabel, Rosado-Ramos, Rita, Rousseau, Caroline, Sagot, Marie France, dos Santos, Claudia Nunes, Schmidt, Markus, Shelenga, Tatiana, Shepherd, Louise, Silva, Ana Rita, da Silva, Marcelo Henriques, Simon, Olivier, Stahlhut, Steen Gustav, Solopova, Ana, Sorokin, Artem, Stewart, Derek, Stougie, Leen, Su, Shang, Thole, Vera, Tikhonova, Olga, Trick, Martin, Vain, Philippe, Veríssimo, André, Vila-Santa, Ana, Vinga, Susana, Vogt, Michael, Wang, Liangsheng, Wang, Lijin, Wei, Wei, Youssef, Sandra, Neves, Ana Rute, Forster, Jochen, Dudnik, Alexey, Almeida, A. Filipa, Andrade, Ricardo, Avila, Barbara, Bañados, Pilar, Barbay, Diane, Bassard, Jean Etienne, Benkoulouche, Mounir, Bott, Michael, Braga, Adelaide, Breitel, Dario, Brennan, Rex, Bulteau, Laurent, Chanforan, Celine, Costa, Inês, Costa, Rafael S., Doostmohammadi, Mahdi, Faria, Nuno, Feng, Chengyong, Fernandes, Armando, Ferreira, Patricia, Ferro, Roberto, Foito, Alexandre, Freitag, Sabine, Garcia, Gonçalo, Gaspar, Paula, Godinho-Pereira, Joana, Hamberger, Björn, Hartmann, András, Heider, Harald, Jardim, Carolina, Julien-Laferriere, Alice, Kallscheuer, Nicolai, Kerbe, Wolfgang, Kuipers, Oscar P., Li, Shanshan, Love, Nicola, Marchetti-Spaccamela, Alberto, Marienhagen, Jan, Martin, Cathie, Mary, Arnaud, Mazurek, Vincent, Meinhart, Camillo, Sevillano, David Méndez, Menezes, Regina, Naesby, Michael, Nørholm, Morten H.H., Okkels, Finn T., Oliveira, Joana, Ottens, Marcel, Parrot, Delphine, Pei, Lei, Rocha, Isabel, Rosado-Ramos, Rita, Rousseau, Caroline, Sagot, Marie France, dos Santos, Claudia Nunes, Schmidt, Markus, Shelenga, Tatiana, Shepherd, Louise, Silva, Ana Rita, da Silva, Marcelo Henriques, Simon, Olivier, Stahlhut, Steen Gustav, Solopova, Ana, Sorokin, Artem, Stewart, Derek, Stougie, Leen, Su, Shang, Thole, Vera, Tikhonova, Olga, Trick, Martin, Vain, Philippe, Veríssimo, André, Vila-Santa, Ana, Vinga, Susana, Vogt, Michael, Wang, Liangsheng, Wang, Lijin, Wei, Wei, Youssef, Sandra, Neves, Ana Rute, and Forster, Jochen
Abstract: BACterial Hosts for production of Bioactive phenolics from bERRY fruits (BacHBerry) was a 3-year project funded by the Seventh Framework Programme (FP7) of the European Union that ran between November 2013 and October 2016. The overall aim of the project was to establish a sustainable and economically-feasible strategy for the production of novel high-value phenolic compounds isolated from berry fruits using bacterial platforms. The project aimed at covering all stages of the discovery and pre-commercialization process, including berry collection, screening and characterization of their bioactive components, identification and functional characterization of the corresponding biosynthetic pathways, and construction of Gram-positive bacterial cell factories producing phenolic compounds. Further activities included optimization of polyphenol extraction methods from bacterial cultures, scale-up of production by fermentation up to pilot scale, as well as societal and economic analyses of the processes. This review article summarizes some of the key findings obtained throughout the duration of the project.
Published: 2018
Full Text: View/download PDF

24. BacHBerry:BACterial hosts for production of bioactive phenolics from bERRY fruits

Author: Dudnik, Alexey, Almeida, A. Filipa, Andrade, Ricardo, Avila, Barbara, Bañados, Pilar, Barbay, Diane, Bassard, Jean-Étienne André, Benkoulouche, Mounir, Bott, Michael, Braga, Adelaide, Breitel, Dario, Brennan, Rex, Bulteau, Laurent, Chanforan, Celine, Costa, Inês, Costa, Rafael S., Doostmohammadi, Mahdi, Faria, Nuno, Feng, Chengyong, Fernandes, Armando, Ferreira, Patricia, Ferro, Roberto, Foito, Alexandre, Freitag, Sabine, Garcia, Gonçalo, Gaspar, Paula, Godinho-Pereira, Joana, Hamberger, Björn Robert, Hartmann, András, Heider, Harald, Jardim, Carolina, Julien-Laferriere, Alice, Kallscheuer, Nicolai, Kerbe, Wolfgang, Kuipers, Oscar P., Li, Shanshan, Love, Nicola, Marchetti-Spaccamela, Alberto, Marienhagen, Jan, Martin, Cathie, Mary, Arnaud, Mazurek, Vincent, Meinhart, Camillo, Sevillano, David Méndez, Menezes, Regina, Naesby, Michael, Nørholm, Morten H.H., Okkels, Finn T., Stahlhut, Steen Gustav, Vogt, Michael, Dudnik, Alexey, Almeida, A. Filipa, Andrade, Ricardo, Avila, Barbara, Bañados, Pilar, Barbay, Diane, Bassard, Jean-Étienne André, Benkoulouche, Mounir, Bott, Michael, Braga, Adelaide, Breitel, Dario, Brennan, Rex, Bulteau, Laurent, Chanforan, Celine, Costa, Inês, Costa, Rafael S., Doostmohammadi, Mahdi, Faria, Nuno, Feng, Chengyong, Fernandes, Armando, Ferreira, Patricia, Ferro, Roberto, Foito, Alexandre, Freitag, Sabine, Garcia, Gonçalo, Gaspar, Paula, Godinho-Pereira, Joana, Hamberger, Björn Robert, Hartmann, András, Heider, Harald, Jardim, Carolina, Julien-Laferriere, Alice, Kallscheuer, Nicolai, Kerbe, Wolfgang, Kuipers, Oscar P., Li, Shanshan, Love, Nicola, Marchetti-Spaccamela, Alberto, Marienhagen, Jan, Martin, Cathie, Mary, Arnaud, Mazurek, Vincent, Meinhart, Camillo, Sevillano, David Méndez, Menezes, Regina, Naesby, Michael, Nørholm, Morten H.H., Okkels, Finn T., Stahlhut, Steen Gustav, and Vogt, Michael
Abstract: BACterial Hosts for production of Bioactive phenolics from bERRY fruits (BacHBerry) was a 3-year project funded by the Seventh Framework Programme (FP7) of the European Union that ran between November 2013 and October 2016. The overall aim of the project was to establish a sustainable and economically-feasible strategy for the production of novel high-value phenolic compounds isolated from berry fruits using bacterial platforms. The project aimed at covering all stages of the discovery and pre-commercialization process, including berry collection, screening and characterization of their bioactive components, identification and functional characterization of the corresponding biosynthetic pathways, and construction of Gram-positive bacterial cell factories producing phenolic compounds. Further activities included optimization of polyphenol extraction methods from bacterial cultures, scale-up of production by fermentation up to pilot scale, as well as societal and economic analyses of the processes. This review article summarizes some of the key findings obtained throughout the duration of the project.
Published: 2018

25. In vivo selection of sfGFP variants with improved and reliable functionality in industrially important thermophilic bacteria

Author: Frenzel, Elrike, Legebeke, Jelmer, Van Stralen, Atze, Van Kranenburg, Richard, Kuipers, Oscar P., Frenzel, Elrike, Legebeke, Jelmer, Van Stralen, Atze, Van Kranenburg, Richard, and Kuipers, Oscar P.
Abstract: Background: Fluorescent reporter proteins (FP) have become an indispensable tool for the optimization of microbial cell factories and in synthetic biology per se. The applicability of the currently available FPs is, however, constrained by species-dependent performance and misfolding at elevated temperatures. To obtain functional reporters for thermophilic, biotechnologically important bacteria such as Parageobacillus thermoglucosidasius, an in vivo screening approach based on a mutational library of superfolder GFP was applied. Results: Flow cytometry-based benchmarking of a set of GFPs, sfGFPs and species-specific codon-optimized variants revealed that none of the proteins was satisfyingly detectable in P. thermoglucosidasius at its optimal growth temperature of 60 °C. An undirected mutagenesis approach coupled to fluorescence-activated cell sorting allowed the isolation of sfGFP variants that were extremely well expressed in the chassis background at 60 °C. Notably, a few nucleotide substitutions, including silent mutations, significantly improved the functionality and brightness. The best mutant sfGFP(N39D/A179A) showed an 885-fold enhanced mean fluorescence intensity (MFI) at 60 °C and is the most reliable reporter protein with respect to cell-to-cell variation and signal intensity reported so far. The in vitro spectral and thermostability properties were unaltered as compared to the parental sfGFP protein, strongly indicating that the combination of the amino acid exchange and an altered translation or folding speed, or protection from degradation, contribute to the strongly improved in vivo performance. Furthermore, sfGFP(N39D/A179A) and the newly developed cyan and yellow derivatives were successfully used for labeling several industrially relevant thermophilic bacilli, thus proving their broad applicability. Conclusions: This study illustrates the power of in vivo isolation of thermostable proteins to obtain reporters for highly efficient fluorescence label
Published: 2018

26. BacHBerry:: BACterial Hosts for production of Bioactive phenolics from bERRY fruits

Author: Dudnik, Alexey, Almeida, A. Filipa, Andrade, Ricardo, Avila, Barbara, Bañados, Pilar, Barbay, Diane, Bassard, Jean Etienne, Benkoulouche, Mounir, Bott, Michael, Braga, Adelaide, Breitel, Dario, Brennan, Rex, Bulteau, Laurent, Chanforan, Celine, Costa, Inês, Costa, Rafael S., Doostmohammadi, Mahdi, Faria, Nuno, Feng, Chengyong, Fernandes, Armando, Ferreira, Patricia, Ferro, Roberto, Foito, Alexandre, Freitag, Sabine, Garcia, Gonçalo, Gaspar, Paula, Godinho-Pereira, Joana, Hamberger, Björn, Hartmann, András, Heider, Harald, Jardim, Carolina, Julien-Laferriere, Alice, Kallscheuer, Nicolai, Kerbe, Wolfgang, Kuipers, Oscar P., Li, Shanshan, Love, Nicola, Marchetti-Spaccamela, Alberto, Marienhagen, Jan, Martin, Cathie, Mary, Arnaud, Mazurek, Vincent, Meinhart, Camillo, Sevillano, David Méndez, Menezes, Regina, Naesby, Michael, Nørholm, Morten H.H., Okkels, Finn T., Oliveira, Joana, Ottens, Marcel, Parrot, Delphine, Pei, Lei, Rocha, Isabel, Rosado-Ramos, Rita, Rousseau, Caroline, Sagot, Marie France, Dos Santos, Claudia Nunes, Schmidt, Markus, Shelenga, Tatiana, Shepherd, Louise, Silva, Ana Rita, da Silva, Marcelo Henriques, Simon, Olivier, Stahlhut, Steen Gustav, Solopova, Ana, Sorokin, Artem, Stewart, Derek, Stougie, Leen, Su, Shang, Thole, Vera, Tikhonova, Olga, Trick, Martin, Vain, Philippe, Veríssimo, André, Vila-Santa, Ana, Vinga, Susana, Vogt, Michael, Wang, Liangsheng, Wang, Lijin, Wei, Wei, Youssef, Sandra, Neves, Ana Rute, Forster, Jochen, Dudnik, Alexey, Almeida, A. Filipa, Andrade, Ricardo, Avila, Barbara, Bañados, Pilar, Barbay, Diane, Bassard, Jean Etienne, Benkoulouche, Mounir, Bott, Michael, Braga, Adelaide, Breitel, Dario, Brennan, Rex, Bulteau, Laurent, Chanforan, Celine, Costa, Inês, Costa, Rafael S., Doostmohammadi, Mahdi, Faria, Nuno, Feng, Chengyong, Fernandes, Armando, Ferreira, Patricia, Ferro, Roberto, Foito, Alexandre, Freitag, Sabine, Garcia, Gonçalo, Gaspar, Paula, Godinho-Pereira, Joana, Hamberger, Björn, Hartmann, András, Heider, Harald, Jardim, Carolina, Julien-Laferriere, Alice, Kallscheuer, Nicolai, Kerbe, Wolfgang, Kuipers, Oscar P., Li, Shanshan, Love, Nicola, Marchetti-Spaccamela, Alberto, Marienhagen, Jan, Martin, Cathie, Mary, Arnaud, Mazurek, Vincent, Meinhart, Camillo, Sevillano, David Méndez, Menezes, Regina, Naesby, Michael, Nørholm, Morten H.H., Okkels, Finn T., Oliveira, Joana, Ottens, Marcel, Parrot, Delphine, Pei, Lei, Rocha, Isabel, Rosado-Ramos, Rita, Rousseau, Caroline, Sagot, Marie France, Dos Santos, Claudia Nunes, Schmidt, Markus, Shelenga, Tatiana, Shepherd, Louise, Silva, Ana Rita, da Silva, Marcelo Henriques, Simon, Olivier, Stahlhut, Steen Gustav, Solopova, Ana, Sorokin, Artem, Stewart, Derek, Stougie, Leen, Su, Shang, Thole, Vera, Tikhonova, Olga, Trick, Martin, Vain, Philippe, Veríssimo, André, Vila-Santa, Ana, Vinga, Susana, Vogt, Michael, Wang, Liangsheng, Wang, Lijin, Wei, Wei, Youssef, Sandra, Neves, Ana Rute, and Forster, Jochen
Abstract: BACterial Hosts for production of Bioactive phenolics from bERRY fruits (BacHBerry) was a 3-year project funded by the Seventh Framework Programme (FP7) of the European Union that ran between November 2013 and October 2016. The overall aim of the project was to establish a sustainable and economically-feasible strategy for the production of novel high-value phenolic compounds isolated from berry fruits using bacterial platforms. The project aimed at covering all stages of the discovery and pre-commercialization process, including berry collection, screening and characterization of their bioactive components, identification and functional characterization of the corresponding biosynthetic pathways, and construction of Gram-positive bacterial cell factories producing phenolic compounds. Further activities included optimization of polyphenol extraction methods from bacterial cultures, scale-up of production by fermentation up to pilot scale, as well as societal and economic analyses of the processes. This review article summarizes some of the key findings obtained throughout the duration of the project.
Published: 2018

27. Interplay Between Capsule Expression and Uracil Metabolism in Streptococcus pneumoniae D39

Author: Carvalho, Sandra M., Kloosterman, Tomas G., Manzoor, Irfan, Caldas, Jose, Vinga, Susana, Martinussen, Jan, Saraiva, Ligia M., Kuipers, Oscar P., Neves, Ana P., Carvalho, Sandra M., Kloosterman, Tomas G., Manzoor, Irfan, Caldas, Jose, Vinga, Susana, Martinussen, Jan, Saraiva, Ligia M., Kuipers, Oscar P., and Neves, Ana P.
Abstract: Pyrimidine nucleotides play an important role in the biosynthesis of activated nucleotide sugars (NDP-sugars). NDP-sugars are the precursors of structural polysaccharides in bacteria, including capsule, which is a major virulence factor of the human pathogen S. pneumoniae. In this work, we identified a spontaneous non-reversible mutant of strain D39 that displayed a non-producing capsule phenotype. Whole-genome sequencing analysis of this mutant revealed several non-synonymous single base modifications, including in genes of the de novo synthesis of pyrimidines and in the -10 box of capsule operon promoter (Pops). By directed mutagenesis we showed that the point mutation in Pcps was solely responsible for the drastic decrease in capsule expression. We also demonstrated that D39 subjected to uracil deprivation shows increased biomass and decreased Pcps activity and capsule amounts. Importantly, Pcps expression is further decreased by mutating the first gene of the de novo synthesis of pyrimidines, carA. In contrast, the absence of uracil from the culture medium showed no effect on the spontaneous mutant strain. Co-cultivation of the wild-type and the mutant strain indicated a competitive advantage of the spontaneous mutant (non-producing capsule) in medium devoid of uracil. We propose a model in that uracil may act as a signal for the production of different capsule amounts in S. pneumoniae.
Published: 2018

28. Bacterial pathogens, antibiotics and antibiotic resistance : Editorial

Author: Banin, Ehud, Hughes, Diarmaid, Kuipers, Oscar P., Banin, Ehud, Hughes, Diarmaid, and Kuipers, Oscar P.
Published: 2017
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29. Bacterial gangs: United and strong by means of quorum sensing

Author: Kuipers, Oscar P., Kovács, Ákos T., Kuipers, Oscar P., and Kovács, Ákos T.
Abstract: Microorganisms can effectively communicate with each other. They share information about their community size (quorum), and thereby their nutrient requirement, then take appropriate action such as moving away. They use signalling molecules to coordinate their behaviour. These compounds, like similar molecules in humans, are called pheromones.
Published: 2017

30. From Cell Death to Metabolism: Holin-Antiholin Homologues with New Functions

Author: van den Esker, Marielle H., Kovács, Ákos T., Kuipers, Oscar P., van den Esker, Marielle H., Kovács, Ákos T., and Kuipers, Oscar P.
Abstract: Programmed cell death in bacteria is generally triggered by membrane proteins with functions analogous to those of bacteriophage holins: they disrupt the membrane potential, whereas antiholins antagonize this process. The holin-like class of proteins is present in all three domains of life, but their functions can be different, depending on the species. Using a series of biochemical and genetic approaches, in a recent article in mBio, Charbonnier et al. (mBio 8:e00976-17, 2017, https://doi.org/10.1128/mBio.00976-17) demonstrate that the antiholin homologue in Bacillus subtilis transports pyruvate and is regulated in an unconventional way by its substrate molecule. Here, we discuss the connection between cell death and metabolism in various bacteria carrying genes encoding these holin-antiholin analogues and place the recent study by Charbonnier et al. in an evolutionary context.
Published: 2017

31. Regulation of Cell Wall Plasticity by Nucleotide Metabolism in Lactococcus lactis

Author: UCL - SST/ISV - Institut des sciences de la vie, Solopova, Ana, Formosa, Cécile, Courtin, Pascal, Furlan, Sylviane, Veiga, Patrick, Péchoux, Christine, Armalyte, Julija, Sadauskas, Mikas, Kok, Jan, Hols, Pascal, Dufrêne, Yves, Kuipers, Oscar P., Chapot-Chartier, Marie-Pierre, Kulakauskas, Saulius, UCL - SST/ISV - Institut des sciences de la vie, Solopova, Ana, Formosa, Cécile, Courtin, Pascal, Furlan, Sylviane, Veiga, Patrick, Péchoux, Christine, Armalyte, Julija, Sadauskas, Mikas, Kok, Jan, Hols, Pascal, Dufrêne, Yves, Kuipers, Oscar P., Chapot-Chartier, Marie-Pierre, and Kulakauskas, Saulius
Abstract: To ensure optimal cell growth and separation and to adapt to environmental parameters, bacteria have to maintain a balance between cell wall (CW) rigidity and flexibility. This can be achieved by a concerted action of peptidoglycan (PG) hydrolases and PG-synthesizing/modifying enzymes. In a search for new regulatory mechanisms responsible for the maintenance of this equilibrium in Lactococcus lactis, we isolated mutants that are resistant to the PG hydrolase lysozyme. We found that 14% of the causative mutations were mapped in the guaA gene, the product of which is involved in purine metabolism. Genetic and transcriptional analyses combined with PG structure determination of the guaA mutant enabled us to reveal the pivotal role of the pyrB gene in the regulation ofCWrigidity.Ourresults indicate that conversion of L-aspartate (L-Asp) to N-carbamoyl-L-aspartate by PyrB may reduce the amount of L-Asp available forPGsynthesis and thus cause the appearance of Asp/Asn-less stem peptides in PG. Such stem peptides do not form PG cross-bridges, resulting in a decrease in PG cross-linking and, consequently, reduced PG thickness and rigidity.Wehypothesize that the concurrent utilization of L-Asp for pyrimidine and PG synthesis may be part of the regulatory scheme, ensuring CW flexibility during exponential growth and rigidity in stationary phase. The fact that L-Asp availability is dependent on nucleotide metabolism, which is tightly regulated in accordance with the growth rate, provides L. lactis cells themeansto ensure optimalCWplasticity without theneedto control the expression of PG synthesis genes.
Published: 2016

32. Linking Bacillus cereus genotypes and carbohydrate utilization capacity

Author: Warda, Alicja K., Siezen, Roland J., Boekhorst, Jos, Wells-Bennik, Marjon H.J., de Jong, Anne, Kuipers, Oscar P., Nierop Groot, Masja N., Abee, Tjakko, Warda, Alicja K., Siezen, Roland J., Boekhorst, Jos, Wells-Bennik, Marjon H.J., de Jong, Anne, Kuipers, Oscar P., Nierop Groot, Masja N., and Abee, Tjakko
Abstract: We characterised carbohydrate utilisation of 20 newly sequenced Bacillus cereus strains isolated from food products and food processing environments and two laboratory strains, B. cereus ATCC 10987 and B. cereus ATCC 14579. Subsequently, genome sequences of these strains were analysed together with 11 additional B. cereus reference genomes to provide an overview of the different types of carbohydrate transporters and utilization systems found in B. cereus strains. The combined application of API tests, defined growth media experiments and comparative genomics enabled us to link the carbohydrate utilisation capacity of 22 B. cereus strains with their genome content and in some cases to the panC phylogenetic grouping. A core set of carbohydrates including glucose, fructose, maltose, trehalose, N-acetyl-glucosamine, and ribose could be used by all strains, whereas utilisation of other carbohydrates like xylose, galactose, and lactose, and typical host-derived carbohydrates such as fucose, mannose, N-acetyl-galactosamine and inositol is limited to a subset of strains. Finally, the roles of selected carbohydrate transporters and utilisation systems in specific niches such as soil, foods and the human host are discussed.
Published: 2016

33. Draft whole-genome sequences of three Lactobacillus plantarum food isolates

Author: Fernandez Ramirez, Monica, Boekhorst, Jos, de Jong, Anne, Kuipers, Oscar P., Abee, Tjakko, Nierop Groot, Masja, Fernandez Ramirez, Monica, Boekhorst, Jos, de Jong, Anne, Kuipers, Oscar P., Abee, Tjakko, and Nierop Groot, Masja
Abstract: Lactobacillus plantarum is a widespread member of the Lactobacillus genus and frequently isolated from spoiled acidified food products. Here, we report the draft genome sequences of three L. plantarum food isolates.
Published: 2016

34. Draft whole-genome sequences of 11 Bacillus cereus food isolates

Author: Hayrapetyan, Hasmik, Boekhorst, Jos, de Jong, Anne, Kuipers, Oscar P., Nierop Groot, Masja N., Abee, Tjakko, Hayrapetyan, Hasmik, Boekhorst, Jos, de Jong, Anne, Kuipers, Oscar P., Nierop Groot, Masja N., and Abee, Tjakko
Abstract: Bacillus cereus is a foodborne pathogen causing emetic and diarrheal-type syndromes. Here, we report the whole-genome sequences of 11 B. cereus food isolates.
Published: 2016

35. Bacillus subtilis attachment to Aspergillus niger hyphae results in mutually altered metabolism

Author: Molecular Plant Physiology, Molecular Microbiology, Dep Biologie, Sub Molecular Microbiology, Sub Molecular Plant Physiology, Benoit, Isabelle, van den Esker, Marielle H., Patyshakuliyeva, Aleksandrina, Mattern, Derek J., Blei, Felix, Zhou, Miaomiao, Dijksterhuis, Jan, Brakhage, Axel A., Kuipers, Oscar P., de Vries, Ronald P., Kovács, Ákos T., Molecular Plant Physiology, Molecular Microbiology, Dep Biologie, Sub Molecular Microbiology, Sub Molecular Plant Physiology, Benoit, Isabelle, van den Esker, Marielle H., Patyshakuliyeva, Aleksandrina, Mattern, Derek J., Blei, Felix, Zhou, Miaomiao, Dijksterhuis, Jan, Brakhage, Axel A., Kuipers, Oscar P., de Vries, Ronald P., and Kovács, Ákos T.
Published: 2015

36. Minimum Information about a Biosynthetic Gene cluster: commentary

Author: Medema, Marnix H, Kottmann, Renzo, Yilmaz, Pelin, Cummings, Matthew, Biggins, John B, Blin, Kai, de Bruijn, Irene, Chooi, Yit Heng, Claesen, Jan, Coates, R Cameron, Cruz-Morales, Pablo, Duddela, Srikanth, Dusterhus, Stephanie, Edwards, Daniel J, Fewer, David P, Garg, Neha, Geiger, Christoph, Gomez-Escribano, Juan Pablo, Greule, Anja, Hadjithomas, Michalis, Haines, Anthony S, Helfrich, Eric J N, Hillwig, Matthew L, Ishida, Keishi, Jones, Adam C, Jones, Carla S, Jungmann, Katrin, Kegler, Carsten, Kim, Hyun Uk, Kotter, Peter, Krug, Daniel, Masschelein, Joleen, Melnik, Alexey V, Mantovani, Simone M, Monroe, Emily A, Moore, Marcus, Moss, Nathan, Nutzmann, Hans-Wilhelm, Pan, Guohui, Pati, Amrita, Petras, Daniel, Reen, F Jerry, Rosconi, Federico, Rui, Zhe, Tian, Zhenhua, Tobias, Nicholas J, Tsunematsu, Yuta, Wiemann, Philipp, Wyckoff, Elizabeth, Yan, Xiaohui, Yim, Grace, Yu, Fengan, Xie, Yunchang, Aigle, Bertrand, Apel, Alexander K, Balibar, Carl J, Balskus, Emily P, Barona-Gomez, Francisco, Bechthold, Andreas, Bode, Helge B, Borriss, Rainer, Brady, Sean F, Brakhage, Axel A, Caffrey, Patrick, Cheng, Yi-Qiang, Clardy, Jon, Cox, Russell J, De Mot, Rene, Donadio, Stefano, Donia, Mohamed S, van der Donk, Wilfred A, Dorrestein, Pieter C, Doyle, Sean, Driessen, Arnold J M, Ehling-Schulz, Monika, Entian, Karl-Dieter, Fischbach, Michael A, Gerwick, Lena, Gerwick, William H, Gross, Harald, Gust, Bertolt, Hertweck, Christian, Hofte, Monica, Jensen, Susan E, Ju, Jianhua, Katz, Leonard, Kaysser, Leonard, Klassen, Jonathan L, Keller, Nancy P, Kormanec, Jan, Kuipers, Oscar P, Kuzuyama, Tomohisa, Kyrpides, Nikos C, Kwon, Hyung-Jin, Lautru, Sylvie, Lavigne, Rob, Lee, Chia Y, Linquan, Bai, Liu, Xinyu, Liu, Wen, Luzhetskyy, Andriy, Mahmud, Taifo, Mast, Yvonne, Mendez, Carmen, Metsa-Ketela, Mikko, Micklefield, Jason, Mitchell, Douglas A, Moore, Bradley S, Moreira, Leonilde M, Muller, Rolf, Neilan, Brett A, Nett, Markus, Nielsen, Jens, O'Gara, Fergal, Oikawa, Hideaki, Osbourn, Anne, Osburne, Marcia S, Ostash, Bohdan, Payne, Shelley M, Pernodet, Jean-Luc, Petricek, Miroslav, Piel, Jorn, Ploux, Olivier, Raaijmakers, Jos M, Salas, Jose A, Schmitt, Esther K, Scott, Barry, Seipke, Ryan F, Shen, Ben, Sherman, David H, Sivonen, Kaarina, Smanski, Michael J, Sosio, Margherita, Stegmann, Evi, Sussmuth, Roderich D, Tahlan, Kapil, Thomas, Christopher M, Tang, Yi, Truman, Andrew W, Viaud, Muriel, Walton, Jonathan D, Walsh, Christopher T, Weber, Tilmann, van Wezel, Gilles P, Wilkinson, Barrie, Willey, Joanne M, Wohlleben, Wolfgang, Wright, Gerard D, Ziemert, Nadine, Zhang, Changsheng, Zotchev, Sergey B, Breitling, Rainer, Takano, Eriko, Glockner, Frank Oliver, Medema, Marnix H, Kottmann, Renzo, Yilmaz, Pelin, Cummings, Matthew, Biggins, John B, Blin, Kai, de Bruijn, Irene, Chooi, Yit Heng, Claesen, Jan, Coates, R Cameron, Cruz-Morales, Pablo, Duddela, Srikanth, Dusterhus, Stephanie, Edwards, Daniel J, Fewer, David P, Garg, Neha, Geiger, Christoph, Gomez-Escribano, Juan Pablo, Greule, Anja, Hadjithomas, Michalis, Haines, Anthony S, Helfrich, Eric J N, Hillwig, Matthew L, Ishida, Keishi, Jones, Adam C, Jones, Carla S, Jungmann, Katrin, Kegler, Carsten, Kim, Hyun Uk, Kotter, Peter, Krug, Daniel, Masschelein, Joleen, Melnik, Alexey V, Mantovani, Simone M, Monroe, Emily A, Moore, Marcus, Moss, Nathan, Nutzmann, Hans-Wilhelm, Pan, Guohui, Pati, Amrita, Petras, Daniel, Reen, F Jerry, Rosconi, Federico, Rui, Zhe, Tian, Zhenhua, Tobias, Nicholas J, Tsunematsu, Yuta, Wiemann, Philipp, Wyckoff, Elizabeth, Yan, Xiaohui, Yim, Grace, Yu, Fengan, Xie, Yunchang, Aigle, Bertrand, Apel, Alexander K, Balibar, Carl J, Balskus, Emily P, Barona-Gomez, Francisco, Bechthold, Andreas, Bode, Helge B, Borriss, Rainer, Brady, Sean F, Brakhage, Axel A, Caffrey, Patrick, Cheng, Yi-Qiang, Clardy, Jon, Cox, Russell J, De Mot, Rene, Donadio, Stefano, Donia, Mohamed S, van der Donk, Wilfred A, Dorrestein, Pieter C, Doyle, Sean, Driessen, Arnold J M, Ehling-Schulz, Monika, Entian, Karl-Dieter, Fischbach, Michael A, Gerwick, Lena, Gerwick, William H, Gross, Harald, Gust, Bertolt, Hertweck, Christian, Hofte, Monica, Jensen, Susan E, Ju, Jianhua, Katz, Leonard, Kaysser, Leonard, Klassen, Jonathan L, Keller, Nancy P, Kormanec, Jan, Kuipers, Oscar P, Kuzuyama, Tomohisa, Kyrpides, Nikos C, Kwon, Hyung-Jin, Lautru, Sylvie, Lavigne, Rob, Lee, Chia Y, Linquan, Bai, Liu, Xinyu, Liu, Wen, Luzhetskyy, Andriy, Mahmud, Taifo, Mast, Yvonne, Mendez, Carmen, Metsa-Ketela, Mikko, Micklefield, Jason, Mitchell, Douglas A, Moore, Bradley S, Moreira, Leonilde M, Muller, Rolf, Neilan, Brett A, Nett, Markus, Nielsen, Jens, O'Gara, Fergal, Oikawa, Hideaki, Osbourn, Anne, Osburne, Marcia S, Ostash, Bohdan, Payne, Shelley M, Pernodet, Jean-Luc, Petricek, Miroslav, Piel, Jorn, Ploux, Olivier, Raaijmakers, Jos M, Salas, Jose A, Schmitt, Esther K, Scott, Barry, Seipke, Ryan F, Shen, Ben, Sherman, David H, Sivonen, Kaarina, Smanski, Michael J, Sosio, Margherita, Stegmann, Evi, Sussmuth, Roderich D, Tahlan, Kapil, Thomas, Christopher M, Tang, Yi, Truman, Andrew W, Viaud, Muriel, Walton, Jonathan D, Walsh, Christopher T, Weber, Tilmann, van Wezel, Gilles P, Wilkinson, Barrie, Willey, Joanne M, Wohlleben, Wolfgang, Wright, Gerard D, Ziemert, Nadine, Zhang, Changsheng, Zotchev, Sergey B, Breitling, Rainer, Takano, Eriko, and Glockner, Frank Oliver
Abstract: A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
Published: 2015

37. Bacillus subtilis attachment to Aspergillus niger hyphae results in mutually altered metabolism

Author: Molecular Plant Physiology, Molecular Microbiology, Dep Biologie, Sub Molecular Microbiology, Sub Molecular Plant Physiology, Benoit, Isabelle, van den Esker, Marielle H., Patyshakuliyeva, Aleksandrina, Mattern, Derek J., Blei, Felix, Zhou, Miaomiao, Dijksterhuis, Jan, Brakhage, Axel A., Kuipers, Oscar P., de Vries, Ronald P., Kovács, Ákos T., Molecular Plant Physiology, Molecular Microbiology, Dep Biologie, Sub Molecular Microbiology, Sub Molecular Plant Physiology, Benoit, Isabelle, van den Esker, Marielle H., Patyshakuliyeva, Aleksandrina, Mattern, Derek J., Blei, Felix, Zhou, Miaomiao, Dijksterhuis, Jan, Brakhage, Axel A., Kuipers, Oscar P., de Vries, Ronald P., and Kovács, Ákos T.
Published: 2015

38. Bacillus subtilis attachment to Aspergillus niger hyphae results in mutually altered metabolism

Author: Molecular Plant Physiology, Molecular Microbiology, Dep Biologie, Sub Molecular Microbiology, Sub Molecular Plant Physiology, Benoit, Isabelle, van den Esker, Marielle H., Patyshakuliyeva, Aleksandrina, Mattern, Derek J., Blei, Felix, Zhou, Miaomiao, Dijksterhuis, Jan, Brakhage, Axel A., Kuipers, Oscar P., de Vries, Ronald P., Kovács, Ákos T., Molecular Plant Physiology, Molecular Microbiology, Dep Biologie, Sub Molecular Microbiology, Sub Molecular Plant Physiology, Benoit, Isabelle, van den Esker, Marielle H., Patyshakuliyeva, Aleksandrina, Mattern, Derek J., Blei, Felix, Zhou, Miaomiao, Dijksterhuis, Jan, Brakhage, Axel A., Kuipers, Oscar P., de Vries, Ronald P., and Kovács, Ákos T.
Published: 2015

39. Minimum Information about a Biosynthetic Gene cluster: commentary

Author: Medema, Marnix H, Kottmann, Renzo, Yilmaz, Pelin, Cummings, Matthew, Biggins, John B, Blin, Kai, de Bruijn, Irene, Chooi, Yit Heng, Claesen, Jan, Coates, R Cameron, Cruz-Morales, Pablo, Duddela, Srikanth, Dusterhus, Stephanie, Edwards, Daniel J, Fewer, David P, Garg, Neha, Geiger, Christoph, Gomez-Escribano, Juan Pablo, Greule, Anja, Hadjithomas, Michalis, Haines, Anthony S, Helfrich, Eric J N, Hillwig, Matthew L, Ishida, Keishi, Jones, Adam C, Jones, Carla S, Jungmann, Katrin, Kegler, Carsten, Kim, Hyun Uk, Kotter, Peter, Krug, Daniel, Masschelein, Joleen, Melnik, Alexey V, Mantovani, Simone M, Monroe, Emily A, Moore, Marcus, Moss, Nathan, Nutzmann, Hans-Wilhelm, Pan, Guohui, Pati, Amrita, Petras, Daniel, Reen, F Jerry, Rosconi, Federico, Rui, Zhe, Tian, Zhenhua, Tobias, Nicholas J, Tsunematsu, Yuta, Wiemann, Philipp, Wyckoff, Elizabeth, Yan, Xiaohui, Yim, Grace, Yu, Fengan, Xie, Yunchang, Aigle, Bertrand, Apel, Alexander K, Balibar, Carl J, Balskus, Emily P, Barona-Gomez, Francisco, Bechthold, Andreas, Bode, Helge B, Borriss, Rainer, Brady, Sean F, Brakhage, Axel A, Caffrey, Patrick, Cheng, Yi-Qiang, Clardy, Jon, Cox, Russell J, De Mot, Rene, Donadio, Stefano, Donia, Mohamed S, van der Donk, Wilfred A, Dorrestein, Pieter C, Doyle, Sean, Driessen, Arnold J M, Ehling-Schulz, Monika, Entian, Karl-Dieter, Fischbach, Michael A, Gerwick, Lena, Gerwick, William H, Gross, Harald, Gust, Bertolt, Hertweck, Christian, Hofte, Monica, Jensen, Susan E, Ju, Jianhua, Katz, Leonard, Kaysser, Leonard, Klassen, Jonathan L, Keller, Nancy P, Kormanec, Jan, Kuipers, Oscar P, Kuzuyama, Tomohisa, Kyrpides, Nikos C, Kwon, Hyung-Jin, Lautru, Sylvie, Lavigne, Rob, Lee, Chia Y, Linquan, Bai, Liu, Xinyu, Liu, Wen, Luzhetskyy, Andriy, Mahmud, Taifo, Mast, Yvonne, Mendez, Carmen, Metsa-Ketela, Mikko, Micklefield, Jason, Mitchell, Douglas A, Moore, Bradley S, Moreira, Leonilde M, Muller, Rolf, Neilan, Brett A, Nett, Markus, Nielsen, Jens, O'Gara, Fergal, Oikawa, Hideaki, Osbourn, Anne, Osburne, Marcia S, Ostash, Bohdan, Payne, Shelley M, Pernodet, Jean-Luc, Petricek, Miroslav, Piel, Jorn, Ploux, Olivier, Raaijmakers, Jos M, Salas, Jose A, Schmitt, Esther K, Scott, Barry, Seipke, Ryan F, Shen, Ben, Sherman, David H, Sivonen, Kaarina, Smanski, Michael J, Sosio, Margherita, Stegmann, Evi, Sussmuth, Roderich D, Tahlan, Kapil, Thomas, Christopher M, Tang, Yi, Truman, Andrew W, Viaud, Muriel, Walton, Jonathan D, Walsh, Christopher T, Weber, Tilmann, van Wezel, Gilles P, Wilkinson, Barrie, Willey, Joanne M, Wohlleben, Wolfgang, Wright, Gerard D, Ziemert, Nadine, Zhang, Changsheng, Zotchev, Sergey B, Breitling, Rainer, Takano, Eriko, Glockner, Frank Oliver, Medema, Marnix H, Kottmann, Renzo, Yilmaz, Pelin, Cummings, Matthew, Biggins, John B, Blin, Kai, de Bruijn, Irene, Chooi, Yit Heng, Claesen, Jan, Coates, R Cameron, Cruz-Morales, Pablo, Duddela, Srikanth, Dusterhus, Stephanie, Edwards, Daniel J, Fewer, David P, Garg, Neha, Geiger, Christoph, Gomez-Escribano, Juan Pablo, Greule, Anja, Hadjithomas, Michalis, Haines, Anthony S, Helfrich, Eric J N, Hillwig, Matthew L, Ishida, Keishi, Jones, Adam C, Jones, Carla S, Jungmann, Katrin, Kegler, Carsten, Kim, Hyun Uk, Kotter, Peter, Krug, Daniel, Masschelein, Joleen, Melnik, Alexey V, Mantovani, Simone M, Monroe, Emily A, Moore, Marcus, Moss, Nathan, Nutzmann, Hans-Wilhelm, Pan, Guohui, Pati, Amrita, Petras, Daniel, Reen, F Jerry, Rosconi, Federico, Rui, Zhe, Tian, Zhenhua, Tobias, Nicholas J, Tsunematsu, Yuta, Wiemann, Philipp, Wyckoff, Elizabeth, Yan, Xiaohui, Yim, Grace, Yu, Fengan, Xie, Yunchang, Aigle, Bertrand, Apel, Alexander K, Balibar, Carl J, Balskus, Emily P, Barona-Gomez, Francisco, Bechthold, Andreas, Bode, Helge B, Borriss, Rainer, Brady, Sean F, Brakhage, Axel A, Caffrey, Patrick, Cheng, Yi-Qiang, Clardy, Jon, Cox, Russell J, De Mot, Rene, Donadio, Stefano, Donia, Mohamed S, van der Donk, Wilfred A, Dorrestein, Pieter C, Doyle, Sean, Driessen, Arnold J M, Ehling-Schulz, Monika, Entian, Karl-Dieter, Fischbach, Michael A, Gerwick, Lena, Gerwick, William H, Gross, Harald, Gust, Bertolt, Hertweck, Christian, Hofte, Monica, Jensen, Susan E, Ju, Jianhua, Katz, Leonard, Kaysser, Leonard, Klassen, Jonathan L, Keller, Nancy P, Kormanec, Jan, Kuipers, Oscar P, Kuzuyama, Tomohisa, Kyrpides, Nikos C, Kwon, Hyung-Jin, Lautru, Sylvie, Lavigne, Rob, Lee, Chia Y, Linquan, Bai, Liu, Xinyu, Liu, Wen, Luzhetskyy, Andriy, Mahmud, Taifo, Mast, Yvonne, Mendez, Carmen, Metsa-Ketela, Mikko, Micklefield, Jason, Mitchell, Douglas A, Moore, Bradley S, Moreira, Leonilde M, Muller, Rolf, Neilan, Brett A, Nett, Markus, Nielsen, Jens, O'Gara, Fergal, Oikawa, Hideaki, Osbourn, Anne, Osburne, Marcia S, Ostash, Bohdan, Payne, Shelley M, Pernodet, Jean-Luc, Petricek, Miroslav, Piel, Jorn, Ploux, Olivier, Raaijmakers, Jos M, Salas, Jose A, Schmitt, Esther K, Scott, Barry, Seipke, Ryan F, Shen, Ben, Sherman, David H, Sivonen, Kaarina, Smanski, Michael J, Sosio, Margherita, Stegmann, Evi, Sussmuth, Roderich D, Tahlan, Kapil, Thomas, Christopher M, Tang, Yi, Truman, Andrew W, Viaud, Muriel, Walton, Jonathan D, Walsh, Christopher T, Weber, Tilmann, van Wezel, Gilles P, Wilkinson, Barrie, Willey, Joanne M, Wohlleben, Wolfgang, Wright, Gerard D, Ziemert, Nadine, Zhang, Changsheng, Zotchev, Sergey B, Breitling, Rainer, Takano, Eriko, and Glockner, Frank Oliver
Abstract: A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
Published: 2015

40. Minimum information about a biosynthetic gene cluster

Author: Medema, Marnix H., Kottmann, Renzo, Yilmaz, Pelin, Cummings, Matthew, Biggins, John B., Kai, Blin, de Bruijn, Irene, Chooi, Yit Heng, Claesen, Jan, Coates, R. Cameron, Cruz-Morales, Pablo, Duddela, Srikanth, Düsterhus, Stephanie, Edwards, Daniel J., Fewer, David P., Garg, Neha, Geiger, Christoph, Gomez-Escribano, Juan Pablo, Greule, Anja, Hadjithomas, Michalis, Haines, Anthony S., Helfrich, Eric J. N., Hillwig, Matthew L., Ishida, Keishi, Jones, Adam C., Jones, Carla S., Jungmann, Katrin, Kegler, Carsten, Kim, Hyun Uk, Kötter, Peter, Krug, Daniel, Masschelein, Joleen, Melnik, Alexey V., Mantovan, Simone M., Monroe, Emily A., Moore, Marcus, Moss, Nathan, Nützmann, Hans-Wilhelm, Pan, Guohui, Pati, Amrita, Petras, Daniel, Reen, F. Jerry, Rosconi, Federico, Rui, Zhe, Tian, Zhenhua, Tobias, Nicholas J., Tsunematsu, Yuta, Wiemann, Philipp, Wyckoff, Elizabeth, Yan, Xiaohui, Yim, Grace, Yu, Fengan, Xie, Yunchang, Aigle, Bertrand, Apel, Alexander K., Balibar, Carl J., Balskus, Emily P., Barona-Gómez, Francisco, Bechthold, Andreas, Bode, Helge Björn, Borriss, Rainer, Brady, Sean F., Brakhage, Axel A., Caffrey, Patrick, Cheng, Yi-Qiang, Clardy, Jon, Cox, Russell J., De Mot, René, Donadio, Stefano, Donia, Mohamed S., van der Donk, Wilfred A., Dorrestein, Pieter C., Doyle, Sean, Driessen, Arnold J. M., Ehling-Schulz, Monika, Entian, Karl-Dieter, Fischbach, Michael A., Gerwick, Lena, Gerwick, William H., Gross, Harald, Gust, Bertolt, Hertweck, Christian, Höfte, Monica, Jensen, Susan E., Ju, Jianhua, Katz, Leonard, Kaysser, Leonard, Klassen, Jonathan L., Keller, Nancy P., Kormanec, Jan, Kuipers, Oscar P., Kuzuyama, Tomohisa, Kyrpides, Nikos C., Kwon, Hyung-Jin, Lautru, Sylvie, Lavigne, Rob, Lee, Chia Y., Linquan, Bai, Liu, Xinyu, Liu, Wen, Luzhetskyy, Andriy, Mahmud, Taifo, Mast, Yvonne, Méndez, Carmen, Metsä-Ketelä, Mikko, Micklefield, Jason, Mitchell, Douglas A., Moore, Bradley S., Moreira, Leonilde M., Müller, Rolf, Neilan, Brett A., Nett, Markus, Nielsen, Jens, O’Gara, Fergal, Oikawa, Hideaki, Osbourn, Anne, Osburne, Marcia S., Ostash, Bohdan, Payne, Shelley M., Pernodet, Jean-Luc, Petricek, Miroslav, Piel, Jörn, Ploux, Olivier, Raaijmakers, Jos M., Salas, José A., Schmitt, Esther K., Scott, Barry, Seipke, Ryan F., Shen, Ben, Sherman, David H., Sivonen, Kaarina, Smanski, Michael J., Sosio, Margherita, Stegmann, Evi, Süssmuth, Roderich D., Tahlan, Kapil, Thomas, Christopher M., Tang, Yi, Truman, Andrew W., Viaud, Muriel, Walton, Jonathan D., Walsh, Christopher T., Weber, Tilmann, van Wezel, Gilles P., Wilkinson, Barrie, Willey, Joanne M., Wohlleben, Wolfgang, Wright, Gerard D., Ziemert, Nadine, Zhang, Changsheng, Zotchev, Sergey B., Breitling, Rainer, Takano, Eriko, Glöckner, Frank Oliver, Medema, Marnix H., Kottmann, Renzo, Yilmaz, Pelin, Cummings, Matthew, Biggins, John B., Kai, Blin, de Bruijn, Irene, Chooi, Yit Heng, Claesen, Jan, Coates, R. Cameron, Cruz-Morales, Pablo, Duddela, Srikanth, Düsterhus, Stephanie, Edwards, Daniel J., Fewer, David P., Garg, Neha, Geiger, Christoph, Gomez-Escribano, Juan Pablo, Greule, Anja, Hadjithomas, Michalis, Haines, Anthony S., Helfrich, Eric J. N., Hillwig, Matthew L., Ishida, Keishi, Jones, Adam C., Jones, Carla S., Jungmann, Katrin, Kegler, Carsten, Kim, Hyun Uk, Kötter, Peter, Krug, Daniel, Masschelein, Joleen, Melnik, Alexey V., Mantovan, Simone M., Monroe, Emily A., Moore, Marcus, Moss, Nathan, Nützmann, Hans-Wilhelm, Pan, Guohui, Pati, Amrita, Petras, Daniel, Reen, F. Jerry, Rosconi, Federico, Rui, Zhe, Tian, Zhenhua, Tobias, Nicholas J., Tsunematsu, Yuta, Wiemann, Philipp, Wyckoff, Elizabeth, Yan, Xiaohui, Yim, Grace, Yu, Fengan, Xie, Yunchang, Aigle, Bertrand, Apel, Alexander K., Balibar, Carl J., Balskus, Emily P., Barona-Gómez, Francisco, Bechthold, Andreas, Bode, Helge Björn, Borriss, Rainer, Brady, Sean F., Brakhage, Axel A., Caffrey, Patrick, Cheng, Yi-Qiang, Clardy, Jon, Cox, Russell J., De Mot, René, Donadio, Stefano, Donia, Mohamed S., van der Donk, Wilfred A., Dorrestein, Pieter C., Doyle, Sean, Driessen, Arnold J. M., Ehling-Schulz, Monika, Entian, Karl-Dieter, Fischbach, Michael A., Gerwick, Lena, Gerwick, William H., Gross, Harald, Gust, Bertolt, Hertweck, Christian, Höfte, Monica, Jensen, Susan E., Ju, Jianhua, Katz, Leonard, Kaysser, Leonard, Klassen, Jonathan L., Keller, Nancy P., Kormanec, Jan, Kuipers, Oscar P., Kuzuyama, Tomohisa, Kyrpides, Nikos C., Kwon, Hyung-Jin, Lautru, Sylvie, Lavigne, Rob, Lee, Chia Y., Linquan, Bai, Liu, Xinyu, Liu, Wen, Luzhetskyy, Andriy, Mahmud, Taifo, Mast, Yvonne, Méndez, Carmen, Metsä-Ketelä, Mikko, Micklefield, Jason, Mitchell, Douglas A., Moore, Bradley S., Moreira, Leonilde M., Müller, Rolf, Neilan, Brett A., Nett, Markus, Nielsen, Jens, O’Gara, Fergal, Oikawa, Hideaki, Osbourn, Anne, Osburne, Marcia S., Ostash, Bohdan, Payne, Shelley M., Pernodet, Jean-Luc, Petricek, Miroslav, Piel, Jörn, Ploux, Olivier, Raaijmakers, Jos M., Salas, José A., Schmitt, Esther K., Scott, Barry, Seipke, Ryan F., Shen, Ben, Sherman, David H., Sivonen, Kaarina, Smanski, Michael J., Sosio, Margherita, Stegmann, Evi, Süssmuth, Roderich D., Tahlan, Kapil, Thomas, Christopher M., Tang, Yi, Truman, Andrew W., Viaud, Muriel, Walton, Jonathan D., Walsh, Christopher T., Weber, Tilmann, van Wezel, Gilles P., Wilkinson, Barrie, Willey, Joanne M., Wohlleben, Wolfgang, Wright, Gerard D., Ziemert, Nadine, Zhang, Changsheng, Zotchev, Sergey B., Breitling, Rainer, Takano, Eriko, and Glöckner, Frank Oliver
Abstract: A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
Published: 2015

41. Minimum Information about a Biosynthetic Gene cluster

Author: Medema, M.H., Kottmann, Renzo, Yilmaz, Pelin, Cummings, Matthew, Biggins, J.B., Blin, Kai, De Bruijn, Irene, Chooi, Yit Heng, Claesen, Jan, Coates, R.C., Cruz-Morales, Pablo, Duddela, Srikanth, Düsterhus, Stephanie, Edwards, Daniel J., Fewer, David P., Garg, Neha, Geiger, Christoph, Gomez-Escribano, Juan Pablo, Greule, Anja, Hadjithomas, Michalis, Haines, Anthony S., Helfrich, Eric J.N., Hillwig, Matthew L., Ishida, Keishi, Jones, Adam C., Jones, Carla S., Jungmann, Katrin, Kegler, Carsten, Kim, Hyun Uk, Kötter, Peter, Krug, Daniel, Masschelein, Joleen, Melnik, Alexey V., Mantovani, Simone M., Monroe, Emily A., Moore, Marcus, Moss, Nathan, Nützmann, Hans Wilhelm, Pan, Guohui, Pati, Amrita, Petras, Daniel, Reen, F.J., Rosconi, Federico, Rui, Zhe, Tian, Zhenhua, Tobias, Nicholas J., Tsunematsu, Yuta, Wiemann, Philipp, Wyckoff, Elizabeth, Yan, Xiaohui, Yim, Grace, Yu, Fengan, Xie, Yunchang, Aigle, Bertrand, Apel, Alexander K., Balibar, Carl J., Balskus, Emily P., Barona-Gómez, Francisco, Bechthold, Andreas, Bode, Helge B., Borriss, Rainer, Brady, Sean F., Brakhage, Axel A., Caffrey, Patrick, Cheng, Yi Qiang, Clardy, Jon, Cox, Russell J., De Mot, René, Donadio, Stefano, Donia, Mohamed S., Van Der Donk, Wilfred A., Dorrestein, Pieter C., Doyle, Sean, Driessen, Arnold J.M., Ehling-Schulz, Monika, Entian, Karl Dieter, Fischbach, Michael A., Gerwick, Lena, Gerwick, William H., Gross, Harald, Gust, Bertolt, Hertweck, Christian, Höfte, Monica, Jensen, Susan E., Ju, Jianhua, Katz, Leonard, Kaysser, Leonard, Klassen, Jonathan L., Keller, Nancy P., Kormanec, Jan, Kuipers, Oscar P., Kuzuyama, Tomohisa, Kyrpides, Nikos C., Kwon, Hyung Jin, Lautru, Sylvie, Lavigne, Rob, Lee, Chia Y., Linquan, Bai, Liu, Xinyu, Liu, Wen, Luzhetskyy, Andriy, Mahmud, Taifo, Mast, Yvonne, Méndez, Carmen, Metsä-Ketelä, Mikko, Micklefield, Jason, Mitchell, Douglas A., Moore, Bradley S., Moreira, Leonilde M., Müller, Rolf, Neilan, Brett A., Nett, Markus, Nielsen, Jens, O'Gara, Fergal, Oikawa, Hideaki, Osbourn, Anne, Osburne, Marcia S., Ostash, Bohdan, Payne, Shelley M., Pernodet, Jean Luc, Petricek, Miroslav, Piel, Jörn, Ploux, Olivier, Raaijmakers, Jos M., Salas, José A., Schmitt, Esther K., Scott, Barry, Seipke, Ryan F., Shen, Ben, Sherman, David H., Sivonen, Kaarina, Smanski, Michael J., Sosio, Margherita, Stegmann, Evi, Süssmuth, Roderich D., Tahlan, Kapil, Thomas, Christopher M., Tang, Yi, Truman, Andrew W., Viaud, Muriel, Walton, Jonathan D., Walsh, Christopher T., Weber, Tilmann, Van Wezel, Gilles P., Wilkinson, Barrie, Willey, Joanne M., Wohlleben, Wolfgang, Wright, Gerard D., Ziemert, Nadine, Zhang, Changsheng, Zotchev, Sergey B., Breitling, Rainer, Takano, Eriko, Glöckner, Frank Oliver, Medema, M.H., Kottmann, Renzo, Yilmaz, Pelin, Cummings, Matthew, Biggins, J.B., Blin, Kai, De Bruijn, Irene, Chooi, Yit Heng, Claesen, Jan, Coates, R.C., Cruz-Morales, Pablo, Duddela, Srikanth, Düsterhus, Stephanie, Edwards, Daniel J., Fewer, David P., Garg, Neha, Geiger, Christoph, Gomez-Escribano, Juan Pablo, Greule, Anja, Hadjithomas, Michalis, Haines, Anthony S., Helfrich, Eric J.N., Hillwig, Matthew L., Ishida, Keishi, Jones, Adam C., Jones, Carla S., Jungmann, Katrin, Kegler, Carsten, Kim, Hyun Uk, Kötter, Peter, Krug, Daniel, Masschelein, Joleen, Melnik, Alexey V., Mantovani, Simone M., Monroe, Emily A., Moore, Marcus, Moss, Nathan, Nützmann, Hans Wilhelm, Pan, Guohui, Pati, Amrita, Petras, Daniel, Reen, F.J., Rosconi, Federico, Rui, Zhe, Tian, Zhenhua, Tobias, Nicholas J., Tsunematsu, Yuta, Wiemann, Philipp, Wyckoff, Elizabeth, Yan, Xiaohui, Yim, Grace, Yu, Fengan, Xie, Yunchang, Aigle, Bertrand, Apel, Alexander K., Balibar, Carl J., Balskus, Emily P., Barona-Gómez, Francisco, Bechthold, Andreas, Bode, Helge B., Borriss, Rainer, Brady, Sean F., Brakhage, Axel A., Caffrey, Patrick, Cheng, Yi Qiang, Clardy, Jon, Cox, Russell J., De Mot, René, Donadio, Stefano, Donia, Mohamed S., Van Der Donk, Wilfred A., Dorrestein, Pieter C., Doyle, Sean, Driessen, Arnold J.M., Ehling-Schulz, Monika, Entian, Karl Dieter, Fischbach, Michael A., Gerwick, Lena, Gerwick, William H., Gross, Harald, Gust, Bertolt, Hertweck, Christian, Höfte, Monica, Jensen, Susan E., Ju, Jianhua, Katz, Leonard, Kaysser, Leonard, Klassen, Jonathan L., Keller, Nancy P., Kormanec, Jan, Kuipers, Oscar P., Kuzuyama, Tomohisa, Kyrpides, Nikos C., Kwon, Hyung Jin, Lautru, Sylvie, Lavigne, Rob, Lee, Chia Y., Linquan, Bai, Liu, Xinyu, Liu, Wen, Luzhetskyy, Andriy, Mahmud, Taifo, Mast, Yvonne, Méndez, Carmen, Metsä-Ketelä, Mikko, Micklefield, Jason, Mitchell, Douglas A., Moore, Bradley S., Moreira, Leonilde M., Müller, Rolf, Neilan, Brett A., Nett, Markus, Nielsen, Jens, O'Gara, Fergal, Oikawa, Hideaki, Osbourn, Anne, Osburne, Marcia S., Ostash, Bohdan, Payne, Shelley M., Pernodet, Jean Luc, Petricek, Miroslav, Piel, Jörn, Ploux, Olivier, Raaijmakers, Jos M., Salas, José A., Schmitt, Esther K., Scott, Barry, Seipke, Ryan F., Shen, Ben, Sherman, David H., Sivonen, Kaarina, Smanski, Michael J., Sosio, Margherita, Stegmann, Evi, Süssmuth, Roderich D., Tahlan, Kapil, Thomas, Christopher M., Tang, Yi, Truman, Andrew W., Viaud, Muriel, Walton, Jonathan D., Walsh, Christopher T., Weber, Tilmann, Van Wezel, Gilles P., Wilkinson, Barrie, Willey, Joanne M., Wohlleben, Wolfgang, Wright, Gerard D., Ziemert, Nadine, Zhang, Changsheng, Zotchev, Sergey B., Breitling, Rainer, Takano, Eriko, and Glöckner, Frank Oliver
Abstract: A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
Published: 2015

42. Repeated triggering of sporulation in Bacillus subtilis selects against a protein that affects the timing of cell division

Author: Siebring, Jeroen, Elema, Matthijs J. H., Vega, Fatima Drubi, Kovacs, Akos T., Haccou, Patsy, Kuipers, Oscar P., Siebring, Jeroen, Elema, Matthijs J. H., Vega, Fatima Drubi, Kovacs, Akos T., Haccou, Patsy, and Kuipers, Oscar P.
Abstract: Bacillus subtilis sporulation is a last-resort phenotypical adaptation in response to starvation. The regulatory network underlying this developmental pathway has been studied extensively. However, how sporulation initiation is concerted in relation to the environmental nutrient availability is poorly understood. In a fed-batch fermentation set-up, in which sporulation of ultraviolet (UV)-mutagenized B. subtilis is repeatedly triggered by periods of starvation, fitter strains with mutated tagE evolved. These mutants display altered timing of phenotypical differentiation. The substrate for the wall teichoic acid (WTA)-modifying enzyme TagE, UDP-glucose, has recently been shown to be an intracellular proxy for nutrient availability, and influences the timing of cell division. Here we suggest that UDP-glucose also influences timing of cellular differentiation.
Published: 2014

43. In Bacillus subtilis LutR is part of the global complex regulatory network governing the adaptation to the transition from exponential growth to stationary phase

Author: Zuber, P., İrigül-Sönmez, Öykü, Köroğlu, Türkan E., Öztürk, Büşra, Kovács, Ákos T., Kuipers, Oscar P., Yazgan-Karataş, Ayten, Zuber, P., İrigül-Sönmez, Öykü, Köroğlu, Türkan E., Öztürk, Büşra, Kovács, Ákos T., Kuipers, Oscar P., and Yazgan-Karataş, Ayten
Abstract: The lutR gene, encoding a product resembling a GntR-family transcriptional regulator, has previously been identified as a gene required for the production of the dipeptide antibiotic bacilysin in Bacillus subtilis. To understand the broader regulatory roles of LutR in B. subtilis, we studied the genome-wide effects of a lutR null mutation by combining transcriptional profiling studies using DNA microarrays, reverse transcription quantitative PCR, lacZ fusion analyses and gel mobility shift assays. We report that 65 transcriptional units corresponding to 23 monocistronic units and 42 operons show altered expression levels in lutR mutant cells, as compared with lutR+ wild-type cells in early stationary phase. Among these, 11 single genes and 25 operons are likely to be under direct control of LutR. The products of these genes are involved in a variety of physiological processes associated with the onset of stationary phase in B. subtilis, including degradative enzyme production, antibiotic production and resistance, carbohydrate utilization and transport, nitrogen metabolism, phosphate uptake, fatty acid and phospholipid biosynthesis, protein synthesis and translocation, cell-wall metabolism, energy production, transfer of mobile genetic elements, induction of phage-related genes, sporulation, delay of sporulation and cannibalism, and biofilm formation. Furthermore, an electrophoretic mobility shift assay performed in the presence of both SinR and LutR revealed a close overlap between the LutR and SinR targets. Our data also revealed a significant overlap with the AbrB regulon. Together, these findings reveal that LutR is part of the global complex, interconnected regulatory systems governing adaptation of bacteria to the transition from exponential growth to stationary phase.
Published: 2014

44. Bacillus subtilis attachment to Aspergillus niger hyphae results in mutually altered metabolism

Author: Benoit, Isabelle, van den Esker, Marielle H, Patyshakuliyeva, Aleksandrina, Mattern, Derek J, Blei, Felix, Zhou, M., Dijksterhuis, Jan, Brakhage, Axel A, Kuipers, Oscar P, de Vries, Ronald P, Kovács, Akos T, van den Brink, J., Benoit, Isabelle, van den Esker, Marielle H, Patyshakuliyeva, Aleksandrina, Mattern, Derek J, Blei, Felix, Zhou, M., Dijksterhuis, Jan, Brakhage, Axel A, Kuipers, Oscar P, de Vries, Ronald P, Kovács, Akos T, and van den Brink, J.
Abstract: Interaction between microbes affects the growth, metabolism and differentiation of members of the microbial community. While direct and indirect competition, like antagonism and nutrient consumption have a negative effect on the interacting members of the population, microbes have also evolved in nature not only to fight, but in some cases to adapt to or support each other, while increasing the fitness of the community. The presence of bacteria and fungi in soil results in various interactions including mutualism. Bacilli attach to the plant root and form complex communities in the rhizosphere. Bacillus subtilis, when grown in the presence of Aspergillus niger, interacts similarly with the fungus, by attaching and growing on the hyphae. Based on data obtained in a dual transcriptome experiment, we suggest that both fungi and bacteria alter their metabolism during this interaction. Interestingly, the transcription of genes related to the antifungal and putative antibacterial defence mechanism of B. subtilis and A. niger, respectively, are decreased upon attachment of bacteria to the mycelia. Analysis of the culture supernatant suggests that surfactin production by B. subtilis was reduced when the bacterium was co-cultivated with the fungus. Our experiments provide new insights into the interaction between a bacterium and a fungus.
Published: 2014

45. Bacillus subtilis attachment to Aspergillus niger hyphae results in mutually altered metabolism

Author: Benoit, Isabelle, van den Esker, Marielle H, Patyshakuliyeva, Aleksandrina, Mattern, Derek J, Blei, Felix, Zhou, M., Dijksterhuis, Jan, Brakhage, Axel A, Kuipers, Oscar P, de Vries, Ronald P, Kovács, Akos T, van den Brink, J., Benoit, Isabelle, van den Esker, Marielle H, Patyshakuliyeva, Aleksandrina, Mattern, Derek J, Blei, Felix, Zhou, M., Dijksterhuis, Jan, Brakhage, Axel A, Kuipers, Oscar P, de Vries, Ronald P, Kovács, Akos T, and van den Brink, J.
Abstract: Interaction between microbes affects the growth, metabolism and differentiation of members of the microbial community. While direct and indirect competition, like antagonism and nutrient consumption have a negative effect on the interacting members of the population, microbes have also evolved in nature not only to fight, but in some cases to adapt to or support each other, while increasing the fitness of the community. The presence of bacteria and fungi in soil results in various interactions including mutualism. Bacilli attach to the plant root and form complex communities in the rhizosphere. Bacillus subtilis, when grown in the presence of Aspergillus niger, interacts similarly with the fungus, by attaching and growing on the hyphae. Based on data obtained in a dual transcriptome experiment, we suggest that both fungi and bacteria alter their metabolism during this interaction. Interestingly, the transcription of genes related to the antifungal and putative antibacterial defence mechanism of B. subtilis and A. niger, respectively, are decreased upon attachment of bacteria to the mycelia. Analysis of the culture supernatant suggests that surfactin production by B. subtilis was reduced when the bacterium was co-cultivated with the fungus. Our experiments provide new insights into the interaction between a bacterium and a fungus.
Published: 2014

46. Ribosomally synthesized and post-translationally modified peptide natural products : overview and recommendations for a universal nomenclature

Author: Arnison, Paul G., Bibb, Mervyn J., Bierbaum, Gabriele, Bowers, Albert A., Bugni, Tim S., Bulaj, Grzegorz, Camarero, Julio A., Campopiano, Dominic J., Challis, Gregory L., Clardy, Jon, Cotter, Paul D., Craik, David J., Dawson, Michael, Dittmann, Elke, Donadio, Stefano, Dorrestein, Pieter C., Entian, Karl-Dieter, Fischbach, Michael A., Garavelli, John S., Göransson, Ulf, Gruber, Christian W., Haft, Daniel H., Hemscheidt, Thomas K., Hertweck, Christian, Hill, Colin, Horswill, Alexander R., Jaspars, Marcel, Kelly, Wendy L., Klinman, Judith P., Kuipers, Oscar P., Link, A. James, Liu, Wen, Marahiel, Mohamed A., Mitchell, Douglas A., Moll, Gert N., Moore, Bradley S., Mueller, Rolf, Nair, Satish K., Nes, Ingolf F., Norris, Gillian E., Olivera, Baldomero M., Onaka, Hiroyasu, Patchett, Mark L., Piel, Joern, Reaney, Martin J. T., Rebuffat, Sylvie, Ross, R. Paul, Sahl, Hans-Georg, Schmidt, Eric W., Selsted, Michael E., Severinov, Konstantin, Shen, Ben, Sivonen, Kaarina, Smith, Leif, Stein, Torsten, Suessmuth, Roderich D., Tagg, John R., Tang, Gong-Li, Truman, Andrew W., Vederas, John C., Walsh, Christopher T., Walton, Jonathan D., Wenzel, Silke C., Willey, Joanne M., van der Donk, Wilfred A., Arnison, Paul G., Bibb, Mervyn J., Bierbaum, Gabriele, Bowers, Albert A., Bugni, Tim S., Bulaj, Grzegorz, Camarero, Julio A., Campopiano, Dominic J., Challis, Gregory L., Clardy, Jon, Cotter, Paul D., Craik, David J., Dawson, Michael, Dittmann, Elke, Donadio, Stefano, Dorrestein, Pieter C., Entian, Karl-Dieter, Fischbach, Michael A., Garavelli, John S., Göransson, Ulf, Gruber, Christian W., Haft, Daniel H., Hemscheidt, Thomas K., Hertweck, Christian, Hill, Colin, Horswill, Alexander R., Jaspars, Marcel, Kelly, Wendy L., Klinman, Judith P., Kuipers, Oscar P., Link, A. James, Liu, Wen, Marahiel, Mohamed A., Mitchell, Douglas A., Moll, Gert N., Moore, Bradley S., Mueller, Rolf, Nair, Satish K., Nes, Ingolf F., Norris, Gillian E., Olivera, Baldomero M., Onaka, Hiroyasu, Patchett, Mark L., Piel, Joern, Reaney, Martin J. T., Rebuffat, Sylvie, Ross, R. Paul, Sahl, Hans-Georg, Schmidt, Eric W., Selsted, Michael E., Severinov, Konstantin, Shen, Ben, Sivonen, Kaarina, Smith, Leif, Stein, Torsten, Suessmuth, Roderich D., Tagg, John R., Tang, Gong-Li, Truman, Andrew W., Vederas, John C., Walsh, Christopher T., Walton, Jonathan D., Wenzel, Silke C., Willey, Joanne M., and van der Donk, Wilfred A.
Abstract: This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products. The current knowledge regarding the biosynthesis of the >20 distinct compound classes is also reviewed, and commonalities are discussed.
Published: 2013
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47. Pyruvate Oxidase Influences the Sugar Utilization Pattern and Capsule Production in Streptococcus pneumoniae

Author: Carvalho, Sandra M., Farshchi Andisi, Vahid, Gradstedt, Henrik, Neef, Jolanda, Kuipers, Oscar P., Neves, Ana R., Bijlsma, Jetta J. E., Carvalho, Sandra M., Farshchi Andisi, Vahid, Gradstedt, Henrik, Neef, Jolanda, Kuipers, Oscar P., Neves, Ana R., and Bijlsma, Jetta J. E.
Abstract: Pyruvate oxidase is a key function in the metabolism and lifestyle of many lactic acid bacteria and its activity depends on the presence of environmental oxygen. In Streptococcus pneumoniae the protein has been suggested to play a major role in metabolism and has been implicated in virulence, oxidative stress survival and death in stationary phase. Under semi-aerobic conditions, transcriptomic and metabolite profiling analysis of a spxB mutant grown on glucose showed minor changes compared to the wild type, apart from the significant induction of two operons involved in carbohydrate uptake and processing. This induction leads to a change in the sugar utilization capabilities of the bacterium, as indicated by the analysis of the growth profiles of the D39 parent and spxB mutant on alternative carbohydrates. Metabolic analysis and growth experiments showed that inactivation of SpxB has no effect on the glucose fermentation pattern, except under aerobic conditions. More importantly, we show that mutation of spxB results in the production of increased amounts of capsule, the major virulence factor of S. pneumoniae. Part of this increase can be attributed to induction of capsule operon (cps) transcription. Therefore, we propose that S. pneumoniae utilizes pyruvate oxidase as an indirect sensor of the oxygenation of the environment, resulting in the adaption of its nutritional capability and the amount of capsule to survive in the host.
Published: 2013

48. Benchmarking Various Green Fluorescent Protein Variants in Bacillus subtilis, Streptococcus pneumoniae, and Lactococcus lactis for Live Cell Imaging

Author: Overkamp, Wout, Beilharz, Katrin, Weme, Ruud Detert Oude, Solopova, Ana, Karsens, Harma, Kovacs, Akos T., Kok, Jan, Kuipers, Oscar P., Veening, Jan-Willem, Overkamp, Wout, Beilharz, Katrin, Weme, Ruud Detert Oude, Solopova, Ana, Karsens, Harma, Kovacs, Akos T., Kok, Jan, Kuipers, Oscar P., and Veening, Jan-Willem
Abstract: Green fluorescent protein (GFP) offers efficient ways of visualizing promoter activity and protein localization in vivo, and many different variants are currently available to study bacterial cell biology. Which of these variants is best suited for a certain bacterial strain, goal, or experimental condition is not clear. Here, we have designed and constructed two "superfolder" GFPs with codon adaptation specifically for Bacillus subtilis and Streptococcus pneumoniae and have benchmarked them against five other previously available variants of GFP in B. subtilis, S. pneumoniae, and Lactococcus lactis, using promoter-gfp fusions. Surprisingly, the best-performing GFP under our experimental conditions in B. subtilis was the one codon optimized for S. pneumoniae and vice versa. The data and tools described in this study will be useful for cell biology studies in low-GC-rich Gram-positive bacteria.
Published: 2013

49. AcmD, a homolog of the major autolysin AcmA of Lactococcus lactis, binds to the cell wall and contributes to cell separation and autolysis

Author: Visweswaran, Ganesh Ram R, Steen, Anton, Leenhouts, Kees, Szeliga, Monika, Ruban, Beata, Hesseling-Meinders, Anne, Dijkstra, Bauke W, Kuipers, Oscar P, Kok, Jan, Buist, Girbe, Visweswaran, Ganesh Ram R, Steen, Anton, Leenhouts, Kees, Szeliga, Monika, Ruban, Beata, Hesseling-Meinders, Anne, Dijkstra, Bauke W, Kuipers, Oscar P, Kok, Jan, and Buist, Girbe
Abstract: Lactococcus lactis expresses the homologous glucosaminidases AcmB, AcmC, AcmA and AcmD. The latter two have three C-terminal LysM repeats for peptidoglycan binding. AcmD has much shorter intervening sequences separating the LysM repeats and a lower iso-electric point (4.3) than AcmA (10.3). Under standard laboratory conditions AcmD was mainly secreted into the culture supernatant. An L. lactis acmAacmD double mutant formed longer chains than the acmA single mutant, indicating that AcmD contributes to cell separation. This phenotype could be complemented by plasmid-encoded expression of AcmD in the double mutant. No clear difference in cellular lysis and protein secretion was observed between both mutants. Nevertheless, overexpression of AcmD resulted in increased autolysis when AcmA was present (as in the wild type strain) or when AcmA was added to the culture medium of an AcmA-minus strain. Possibly, AcmD is mainly active within the cell wall, at places where proper conditions are present for its binding and catalytic activity. Various fusion proteins carrying either the three LysM repeats of AcmA or AcmD were used to study and compare their cell wall binding characteristics. Whereas binding of the LysM domain of AcmA took place at pHs ranging from 4 to 8, LysM domain of AcmD seems to bind strongest at pH 4.
Published: 2013

50. DEAD-Box RNA Helicases in Bacillus subtilis Have Multiple Functions and Act Independently from Each Other

Author: Lehnik-Habrink, Martin, Rempeters, Leonie, Kovacs, Akos T., Wrede, Christoph, Baierlein, Claudia, Krebber, Heike, Kuipers, Oscar P., Stuelke, Joerg, Stülke, Jörg, Lehnik-Habrink, Martin, Rempeters, Leonie, Kovacs, Akos T., Wrede, Christoph, Baierlein, Claudia, Krebber, Heike, Kuipers, Oscar P., Stuelke, Joerg, and Stülke, Jörg
Abstract: DEAD-box RNA helicases play important roles in remodeling RNA molecules and in facilitating a variety of RNA-protein interactions that are key to many essential cellular processes. In spite of the importance of RNA, our knowledge about RNA helicases is limited. In this study, we investigated the role of the four DEAD-box RNA helicases in the Gram-positive model organism Bacillus subtilis. A strain deleted of all RNA helicases is able to grow at 37 degrees C but not at lower temperatures. The deletion of cshA, cshB, or yfmL in particular leads to cold-sensitive phenotypes. Moreover, these mutant strains exhibit unique defects in ribosome biogenesis, suggesting distinct functions for the individual enzymes in this process. Based on protein accumulation, severity of the cold-sensitive phenotype, and the interaction with components of the RNA degradosome, CshA is the major RNA helicase of B. subtilis. To unravel the functions of CshA in addition to ribosome biogenesis, we conducted microarray analysis and identified the ysbAB and frlBONMD mRNAs as targets that are strongly affected by the deletion of the cshA gene. Our findings suggest that the different helicases make distinct contributions to the physiology of B. subtilis. Ribosome biogenesis and RNA degradation are two of their major tasks in B. subtilis.
Published: 2013

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