5 results on '"Martin Baunach"'
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2. The Landscape of Recombination Events That Create Nonribosomal Peptide Diversity
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Martin Baunach, Somak Chowdhury, Elke Dittmann, and Pierre Stallforth
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natural products ,nonribosomal peptide synthetases ,Structural diversity ,Computational biology ,Biology ,AcademicSubjects/SCI01180 ,microbial ecology ,01 natural sciences ,Domain (software engineering) ,Evolution, Molecular ,03 medical and health sciences ,Nonribosomal peptide ,evolution ,Genetics ,Peptide Synthases ,Molecular Biology ,Gene ,Ecology, Evolution, Behavior and Systematics ,Discoveries ,030304 developmental biology ,chemistry.chemical_classification ,Recombination, Genetic ,0303 health sciences ,Models, Genetic ,010405 organic chemistry ,AcademicSubjects/SCI01130 ,Multienzyme complexes ,recombination ,0104 chemical sciences ,chemistry ,structural diversity ,Multigene Family ,Selectivity filter ,Peptide Biosynthesis, Nucleic Acid-Independent ,Recombination - Abstract
Nonribosomal peptides (NRP) are crucial molecular mediators in microbial ecology and provide indispensable drugs. Nevertheless, the evolution of the flexible biosynthetic machineries that correlates with the stunning structural diversity of NRPs is poorly understood. Here, we show that recombination is a key driver in the evolution of bacterial NRP synthetase (NRPS) genes across distant bacterial phyla, which has guided structural diversification in a plethora of NRP families by extensive mixing and matching of biosynthesis genes. The systematic dissection of a large number of individual recombination events did not only unveil a striking plurality in the nature and origin of the exchange units but allowed the deduction of overarching principles that enable the efficient exchange of adenylation (A) domain substrates while keeping the functionality of the dynamic multienzyme complexes. In the majority of cases, recombination events have targeted variable portions of the Acore domains, yet domain interfaces and the flexible Asub domain remained untapped. Our results strongly contradict the widespread assumption that adenylation and condensation (C) domains coevolve and significantly challenge the attributed role of C domains as stringent selectivity filter during NRP synthesis. Moreover, they teach valuable lessons on the choice of natural exchange units in the evolution of NRPS diversity, which may guide future engineering approaches.
- Published
- 2021
3. One-Pot Chemoenzymatic Synthesis of Microviridin Analogs Containing Functional Tags
- Author
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Stella Scholz, Sofia Kerestetzopoulou, Vincent Wiebach, Romina Schnegotzki, Bianca Schmid, Emmanuel Reyna‐González, Ling Ding, Roderich D. Süssmuth, Elke Dittmann, and Martin Baunach
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microviridins ,Microviridins ,Serine Proteinase Inhibitors ,Lactams ,Organic Chemistry ,protease inhibitors ,chemoenzymatic synthesis ,Protease inhibitors ,Biochemistry ,Lactones ,RiPPs ,540 Chemie und zugeordnete Wissenschaften ,Molecular Medicine ,Chemoenzymatic synthesis ,synthetic biology ,Peptides ,Protein Processing, Post-Translational ,Molecular Biology ,Synthetic biology ,Peptide Hydrolases - Abstract
Microviridins are a prominent family of ribosomally synthesized and post-translationally modified peptides (RiPPs) featuring characteristic lactone and lactam rings. Their unusual cage-like architecture renders them highly potent serine protease inhibitors of which individual variants specifically inhibit different types of proteases of pharmacological interest. While posttranslational modifications are key for the stability and bioactivity of RiPPs, additional attractive properties can be introduced by functional tags. To date - although highly desirable - no method has been reported to incorporate functional tags in microviridin scaffolds or the overarching class of graspetides. In this study, a chemoenzymatic in vitro platform is used to introduce functional tags in various microviridin variants yielding biotinylated, dansylated or propargylated congeners. This straightforward approach paves the way for customized protease inhibitors with built-in functionalities that can help to unravel the still elusive ecological roles and targets of this remarkable class of compounds and to foster applications based on protease inhibition.
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- 2022
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4. A community resource for paired genomic and metabolomic data mining
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Lars Ridder, Tim S. Bugni, Jamshid Amiri Moghaddam, Florian Huber, Elke Dittmann, Kelly C. Weldon, Louis-Félix Nothias, Douglas Sweeney, Mingxun Wang, Paul R. Jensen, Letícia V. Costa-Lotufo, Christine Beemelmanns, Katherine R. Duncan, Nadine Ziemert, Xuanji Li, Dulce G. Guillén Matus, Chao Du, Neha Garg, Jae Seoun Hur, Elizabeth I. Parkinson, Raphael Reher, Nicholas J. Tobias, Alex A. Blacutt, Emily C Pierce, Michelle Schorn, J. Michael Beman, Simon Rogers, María Victoria Berlanga-Clavero, Martin Baunach, Fan Zhang, Deepa D. Acharya, Harald Gross, Hamada Saad, M. Caroline Roper, Anna Edlund, Jason M. Crawford, Daniel Petras, Alexandra Calteau, Benjamin-Florian Hempel, Seoung Rak Lee, Max Crüsemann, Neil L. Kelleher, Hosein Mohimani, David P. Fewer, Shaurya Chanana, Carmen Saenz, Lena Gerwick, Ki-Hyun Kim, Roderich D. Süssmuth, Jörn Piel, Diego Romero, Marnix H. Medema, Anelize Bauermeister, Christopher Drozd, Regan J. Thomson, Anne Boullie, Michael W. Mullowney, Karine Pires, Andrew C. McAvoy, Alexander A. Aksenov, Saefuddin Aziz, Raquel Castelo-Branco, Julia M. Gauglitz, Mitchell N. Muskat, Bart Cuypers, Emily C. Gentry, Yi Yuan Lee, Eric J. N. Helfrich, Tam Dang, Pieter C. Dorrestein, Liu Cao, Rachel J. Dutton, Gilles P. van Wezel, Helge B. Bode, Margherita Sosio, Asker Daniel Brejnrod, Gajender Aleti, Leonard Kaysser, Amaro E. Trindade-Silva, Willam W. Metcalf, Irina Koester, Tiago Leao, Katherine D. Bauman, Jessica C. Little, Evgenia Glukhov, Ellis C. O’Neill, Justin J. J. van der Hooft, Alyssa M. Demko, Alexander B. Chase, Marc G. Chevrette, Bradley S. Moore, Christian Martin H, Kapil Tahlan, Cameron R. Currie, Allegra T. Aron, Muriel Gugger, Kyo Bin Kang, Víctor J. Carrión, Michael J. Rust, Gabriele M. König, Carlos Molina-Santiago, Søren J. Sørensen, Marianna Iorio, Jean-Claude Dujardin, Daniel Männle, Chung Sub Kim, Laura M. Sanchez, Katherine N. Maloney, Stefan Verhoeven, Tristan de Rond, Wageningen University and Research [Wageningen] (WUR), Netherlands eScience Center, University of Wisconsin-Madison, University of California [San Diego] (UC San Diego), University of California, Leibniz Institute for Natural Product Research and Infection Biology (Hans Knoell Institute), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Jenderal Soedirman University [Purwokerto, Indonesia], Universidade de São Paulo (USP), University of Potsdam, University of California [Merced], Universidad de Málaga [Málaga] = University of Málaga [Málaga], University of California [Riverside] (UCR), Goethe-University Frankfurt am Main, Senckenberg – Leibniz Institution for Biodiversity and Earth System Research - Senckenberg Gesellschaft für Naturforschung, Leibniz Association, Max Planck Institute for Terrestrial Microbiology, Max-Planck-Gesellschaft, Collection des Cyanobactéries, Institut Pasteur [Paris], Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Carnegie Mellon University [Pittsburgh] (CMU), Leiden University, Netherlands Institute of Ecology (NIOO-KNAW), Universidade do Porto, University of Helsinki, Yale University [New Haven], Yale University School of Medicine, University of Antwerp (UA), Institute of Tropical Medicine [Antwerp] (ITM), Technische Universität Berlin (TU), J. Craig Venter Institute [La Jolla, USA] (JCVI), Instituto de Investigaciones Científicas y Servicios de Alta Tecnología [Panama], The research reported in this publication was supported by an ASDI eScience Grant (ASDI.2017.030) fromthe Netherlands eScience Center (to J.J.J.v.d.H. and M.H.M.), a National Institutes of Health (NIH) Genometo Natural Products Network supplementary award (no. U01GM110706 to M.H.M.), a Wageningen GraduateSchool Postdoc Talent Program fellowship (to M.A.S.), a Marie Sklodowska-Curie Individual Fellowship from the European Union (MSCA-IF-EF-ST-897121 to M.A.S.), the National Science Foundation (NSF) (1817955 to L.M.S. and 1817887 to R.J.D.), a Fundaçao para a Ciencia e Tecnologia (FCT) fellowship (SFRH/BD/136367/2018 to R.C.B.), the National Cancer Institute of the NIH (award no. F32CA221327 to M.W.M.), the University of California, San Diego, Scripps Institution of Oceanography, and two grant from the NIH (Awards GM118815 and 107550 to L.G.), and the National Center for Complementary and Integrative Health of the NIH (award no. R01AT009143 to R.J.T. and N.L.K.)., Microbial Ecology (ME), Department of Food and Nutrition, Department of Microbiology, Helsinki Institute of Sustainability Science (HELSUS), Microbial Natural Products, University of California (UC), Universidade de São Paulo = University of São Paulo (USP), University of Potsdam = Universität Potsdam, University of California [Merced] (UC Merced), University of California [Riverside] (UC Riverside), Institut Pasteur [Paris] (IP), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Universiteit Leiden, Universidade do Porto = University of Porto, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Yale School of Medicine [New Haven, Connecticut] (YSM), and Technical University of Berlin / Technische Universität Berlin (TU)
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Databases, Factual ,Bioinformatics ,Systems biology ,Metabolite ,[SDV]Life Sciences [q-bio] ,Genomics ,Computational biology ,Biology ,Genome ,Plan_S-Compliant-OA ,03 medical and health sciences ,chemistry.chemical_compound ,Databases ,Metabolomics ,Bioinformatica ,Metabolome ,Data Mining ,Life Science ,MolEco ,Molecular Biology ,QH426 ,030304 developmental biology ,0303 health sciences ,METABOLÔMICA ,030302 biochemistry & molecular biology ,Comment ,Cell Biology ,DNA ,Computational biology and bioinformatics ,Chemistry ,chemistry ,international ,Community resource ,1182 Biochemistry, cell and molecular biology ,Identification (biology) - Abstract
International audience; Genomics and metabolomics are widely used to explore specialized metabolite diversity. The Paired Omics Data Platform is a community initiative to systematically document links between metabolome and (meta)genome data, aiding identification of natural product biosynthetic origins and metabolite structures.
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- 2021
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- View/download PDF
5. Cryptic indole hydroxylation by a non-canonical terpenoid cyclase parallels bacterial xenobiotic detoxification
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Zhongli Xu, Philipp Baer, Mie Ishida-Ito, Susann Kugel, Srividhya Sundaram, Michael Groll, Martin Baunach, and Christian Hertweck
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0301 basic medicine ,Indoles ,Science ,General Physics and Astronomy ,Lyases ,Hydroxylation ,Indigo Carmine ,Cyclase ,General Biochemistry, Genetics and Molecular Biology ,Article ,Xenobiotics ,Terpene ,03 medical and health sciences ,chemistry.chemical_compound ,Biosynthesis ,Biotransformation ,Bacterial Proteins ,Phylogeny ,Indole test ,chemistry.chemical_classification ,Multidisciplinary ,Bacteria ,Molecular Structure ,Chemistry ,Terpenes ,fungi ,General Chemistry ,Terpenoid ,030104 developmental biology ,Enzyme ,Biochemistry ,Cyclization ,Inactivation, Metabolic ,Flavin-Adenine Dinucleotide - Abstract
Terpenoid natural products comprise a wide range of molecular architectures that typically result from C–C bond formations catalysed by classical type I/II terpene cyclases. However, the molecular diversity of biologically active terpenoids is substantially increased by fully unrelated, non-canonical terpenoid cyclases. Their evolutionary origin has remained enigmatic. Here we report the in vitro reconstitution of an unusual flavin-dependent bacterial indoloterpenoid cyclase, XiaF, together with a designated flavoenzyme-reductase (XiaP) that mediates a key step in xiamycin biosynthesis. The crystal structure of XiaF with bound FADH2 (at 2.4 Å resolution) and phylogenetic analyses reveal that XiaF is, surprisingly, most closely related to xenobiotic-degrading enzymes. Biotransformation assays show that XiaF is a designated indole hydroxylase that can be used for the production of indigo and indirubin. We unveil a cryptic hydroxylation step that sets the basis for terpenoid cyclization and suggest that the cyclase has evolved from xenobiotics detoxification enzymes., The biosynthesis of xiamycin, an antimicrobial bacterial indolosesquiterpenoid, involves an unusual cyclization cascade. Here, the authors characterise the XiaF enzyme, which resembles xenobiont-degrading enzymes and is responsible for a hidden indole hydroxylation step that triggers the cyclization reaction.
- Published
- 2017
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