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1. Antigenic Characterization of Circulating and Emerging SARS-CoV-2 Variants in the U.S. throughout the Delta to Omicron Waves

Author

Di, Han, primary, Pusch, Elizabeth A., additional, Jones, Joyce, additional, Kovacs, Nicholas A., additional, Hassell, Norman, additional, Sheth, Mili, additional, Lynn, Kelly Sabrina, additional, Keller, Matthew W., additional, Wilson, Malania M., additional, Keong, Lisa M., additional, Cui, Dan, additional, Park, So Hee, additional, Chau, Reina, additional, Lacek, Kristine A., additional, Liddell, Jimma D., additional, Kirby, Marie K., additional, Yang, Genyan, additional, Johnson, Monique, additional, Thor, Sharmi, additional, Zanders, Natosha, additional, Feng, Chenchen, additional, Surie, Diya, additional, DeCuir, Jennifer, additional, Lester, Sandra N., additional, Atherton, Lydia, additional, Hicks, Heather, additional, Tamin, Azaibi, additional, Harcourt, Jennifer L., additional, Coughlin, Melissa M., additional, Self, Wesley H., additional, Rhoads, Jillian P., additional, Gibbs, Kevin W., additional, Hager, David N., additional, Shapiro, Nathan I., additional, Exline, Matthew C., additional, Lauring, Adam S., additional, Rambo-Martin, Benjamin, additional, Paden, Clinton R., additional, Kondor, Rebecca J., additional, Lee, Justin S., additional, Barnes, John R., additional, Thornburg, Natalie J., additional, Zhou, Bin, additional, Wentworth, David E., additional, and Davis, Charles Todd, additional

Published
2024
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2. Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants

Author

Welch, Nicole L., Zhu, Meilin, Hua, Catherine, Weller, Juliane, Mirhashemi, Marzieh Ezzaty, Nguyen, Tien G., Mantena, Sreekar, Bauer, Matthew R., Shaw, Bennett M., Ackerman, Cheri M., Thakku, Sri Gowtham, Tse, Megan W., Kehe, Jared, Uwera, Marie-Martine, Eversley, Jacqueline S., Bielwaski, Derek A., McGrath, Graham, Braidt, Joseph, Johnson, Jeremy, Cerrato, Felecia, Moreno, Gage K., Krasilnikova, Lydia A., Petros, Brittany A., Gionet, Gabrielle L., King, Ewa, Huard, Richard C., Jalbert, Samantha K., Cleary, Michael L., Fitzgerald, Nicholas A., Gabriel, Stacey B., Gallagher, Glen R., Smole, Sandra C., Madoff, Lawrence C., Brown, Catherine M., Keller, Matthew W., Wilson, Malania M., Kirby, Marie K., Barnes, John R., Park, Daniel J., Siddle, Katherine J., Happi, Christian T., Hung, Deborah T., Springer, Michael, MacInnis, Bronwyn L., Lemieux, Jacob E., Rosenberg, Eric, Branda, John A., Blainey, Paul C., Sabeti, Pardis C., and Myhrvold, Cameron

Published
2022
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3. In‐field detection and characterization of B/Victoria lineage deletion variant viruses causing early influenza activity and an outbreak in Louisiana, 2019

Author

Shu, Bo, primary, Wilson, Malania M., additional, Keller, Matthew W., additional, Tran, Ha, additional, Sokol, Theresa, additional, Lee, Grace, additional, Rambo‐Martin, Benjamin L., additional, Kirby, Marie K., additional, Hassell, Norman, additional, Haydel, Danielle, additional, Hand, Julie, additional, Wentworth, David E., additional, and Barnes, John R., additional

Published
2024
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4. Multiplex Real-Time Reverse Transcription PCR for Influenza A Virus, Influenza B Virus, and Severe Acute Respiratory Syndrome Coronavirus 2

Author

Shu, Bo, Kirby, Marie K., Davis, William G., Warnes, Christine, Liddell, Jimma, Liu, Ji, Wu, Kai-Hui, Hassell, Norman, Benitez, Alvaro J., Wilson, Malania M., Keller, Matthew W., Rambo-Martin, Benjamin L., Camara, Yamundow, Winter, Jorn, Kondor, Rebecca J., Zhou, Bin, Spies, Stacey, Rose, Laura E., Winchell, Jonas M., Limbago, Brandi M., Wentworth, David E., and Barnes, John R.

Subjects
Influenza -- Diagnosis, Molecular diagnostic techniques -- Usage, Polymerase chain reaction -- Usage, Health
Abstract

An outbreak of pneumonia of unknown etiology in Wuhan, China, was reported to the World Health Organization on December 31, 2019 (1). Researchers determined that the illness, later known as [...]

Published
2021
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5. Targeted amplification and genetic sequencing of the severe acute respiratory syndrome coronavirus 2 surface glycoprotein

Author

Keller, Matthew W., primary, Keong, Lisa M., additional, Rambo-Martin, Benjamin L., additional, Hassell, Norman, additional, Lacek, Kristine A., additional, Wilson, Malania M., additional, Kirby, Marie K., additional, Liddell, Jimma, additional, Owuor, D. Collins, additional, Sheth, Mili, additional, Madden, Joseph, additional, Lee, Justin S., additional, Kondor, Rebecca J., additional, Wentworth, David E., additional, and Barnes, John R., additional

Published
2023
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6. SARS-CoV-2 spike D614G change enhances replication and transmission

Author

Zhou, Bin, Thao, Tran Thi Nhu, Hoffmann, Donata, Taddeo, Adriano, Ebert, Nadine, Labroussaa, Fabien, Pohlmann, Anne, King, Jacqueline, Steiner, Silvio, Kelly, Jenna N., Portmann, Jasmine, Halwe, Nico Joel, Ulrich, Lorenz, Trüeb, Bettina Salome, Fan, Xiaoyu, Hoffmann, Bernd, Wang, Li, Thomann, Lisa, Lin, Xudong, Stalder, Hanspeter, Pozzi, Berta, de Brot, Simone, Jiang, Nannan, Cui, Dan, Hossain, Jaber, Wilson, Malania M., Keller, Matthew W., Stark, Thomas J., Barnes, John R., Dijkman, Ronald, Jores, Joerg, Benarafa, Charaf, Wentworth, David E., Thiel, Volker, and Beer, Martin

Published
2021
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7. Author Correction: Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants

Author

Welch, Nicole L., primary, Zhu, Meilin, additional, Hua, Catherine, additional, Weller, Juliane, additional, Mirhashemi, Marzieh Ezzaty, additional, Nguyen, Tien G., additional, Mantena, Sreekar, additional, Bauer, Matthew R., additional, Shaw, Bennett M., additional, Ackerman, Cheri M., additional, Thakku, Sri Gowtham, additional, Tse, Megan W., additional, Kehe, Jared, additional, Uwera, Marie-Martine, additional, Eversley, Jacqueline S., additional, Bielwaski, Derek A., additional, McGrath, Graham, additional, Braidt, Joseph, additional, Johnson, Jeremy, additional, Cerrato, Felecia, additional, Moreno, Gage K., additional, Krasilnikova, Lydia A., additional, Petros, Brittany A., additional, Gionet, Gabrielle L., additional, King, Ewa, additional, Huard, Richard C., additional, Jalbert, Samantha K., additional, Cleary, Michael L., additional, Fitzgerald, Nicholas A., additional, Gabriel, Stacey B., additional, Gallagher, Glen R., additional, Smole, Sandra C., additional, Madoff, Lawrence C., additional, Brown, Catherine M., additional, Keller, Matthew W., additional, Wilson, Malania M., additional, Kirby, Marie K., additional, Barnes, John R., additional, Park, Daniel J., additional, Siddle, Katherine J., additional, Happi, Christian T., additional, Hung, Deborah T., additional, Springer, Michael, additional, MacInnis, Bronwyn L., additional, Lemieux, Jacob E., additional, Rosenberg, Eric, additional, Branda, John A., additional, Blainey, Paul C., additional, Sabeti, Pardis C., additional, and Myhrvold, Cameron, additional

Published
2023
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8. Targeted Amplification and Genetic Sequencing of the Severe Acute Respiratory Syndrome Coronavirus 2 Surface Glycoprotein

Author

Keller, Matthew W, primary, Keong, Lisa M, additional, Rambo-Martin, Benjamin L, additional, Hassell, Norman, additional, Lacek, Kristine, additional, Wilson, Malania M, additional, Kirby, Marie K, additional, Liddell, Jimma, additional, Owuor, D Collins, additional, Sheth, Mili, additional, Madden, Joseph, additional, Lee, Justin S, additional, Kondor, Rebecca J, additional, Wentworth, David E, additional, and Barnes, John R, additional

Published
2023
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9. Manipulating Fermentation Pathways in the Hyperthermophilic Archaeon Pyrococcus furiosus for Ethanol Production up to 95°C Driven by Carbon Monoxide Oxidation

Author

Lipscomb, Gina L., primary, Crowley, Alexander T., additional, Nguyen, Diep M. N., additional, Keller, Matthew W., additional, O’Quinn, Hailey C., additional, Tanwee, Tania N. N., additional, Vailionis, Jason L., additional, Zhang, Ke, additional, Zhang, Ying, additional, Kelly, Robert M., additional, and Adams, Michael W. W., additional

Published
2023
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14. Extreme Thermophiles as Metabolic Engineering Platforms: Strategies and Current Perspective

Author

Loder, Andrew J., primary, Zeldes, Benjamin M., additional, Conway, Jonathan M., additional, Counts, James A., additional, Straub, Christopher T., additional, Khatibi, Piyum A., additional, Lee, Laura L., additional, Vitko, Nicholas P., additional, Keller, Matthew W., additional, Rhaesa, Amanda M., additional, Rubinstein, Gabe M., additional, Scott, Israel M., additional, Lipscomb, Gina L., additional, Adams, Michael W.W., additional, and Kelly, Robert M., additional

Published
2016
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16. Influenza A Virus Field Surveillance at a Swine-Human Interface

Author

Rambo-Martin, Benjamin L., primary, Keller, Matthew W., additional, Wilson, Malania M., additional, Nolting, Jacqueline M., additional, Anderson, Tavis K., additional, Vincent, Amy L., additional, Bagal, Ujwal R., additional, Jang, Yunho, additional, Neuhaus, Elizabeth B., additional, Davis, C. Todd, additional, Bowman, Andrew S., additional, Wentworth, David E., additional, and Barnes, John R., additional

Published
2020
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18. Multiplex Real-Time Reverse Transcription PCR for Influenza A Virus, Influenza B Virus, and Severe Acute Respiratory Syndrome Coronavirus 2.

Author

Bo Shu, Kirby, Marie K., Davis, William G., Warnes, Christine, Liddell, Jimma, Ji Liu, Kai-Hui Wu, Hassell, Norman, Benitez, Alvaro J., Wilson, Malania M., Keller, Matthew W., Rambo-Martin, Benjamin L., Camara, Yamundow, Winter, Jörn, Kondor, Rebecca J., Bin Zhou, Spies, Stacey, Rose, Laura E., Winchell, Jonas M., and Limbago, Brandi M.

Subjects
INFLUENZA B virus, INFLUENZA viruses, INFLUENZA A virus, COVID-19, INFLUENZA, COVID-19 pandemic
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019, and the outbreak rapidly evolved into the current coronavirus disease pandemic. SARS-CoV-2 is a respiratory virus that causes symptoms similar to those caused by influenza A and B viruses. On July 2, 2020, the US Food and Drug Administration granted emergency use authorization for in vitro diagnostic use of the Influenza SARS-CoV-2 Multiplex Assay. This assay detects influenza A virus at 102.0, influenza B virus at 102.2, and SARS-CoV-2 at 100.3 50% tissue culture or egg infectious dose, or as few as 5 RNA copies/reaction. The simultaneous detection and differentiation of these 3 major pathogens increases overall testing capacity, conserves resources, identifies co-infections, and enables efficient surveillance of influenza viruses and SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Published
2021
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19. Mitigating Pandemic Risk with Influenza A Virus Field Surveillance at a Swine-Human Interface

Author

Rambo-Martin, Benjamin L., primary, Keller, Matthew W., additional, Wilson, Malania M., additional, Nolting, Jacqueline M., additional, Anderson, Tavis K., additional, Vincent, Amy L., additional, Bagal, Ujwal, additional, Jang, Yunho, additional, Neuhaus, Elizabeth B., additional, Davis, C. Todd, additional, Bowman, Andrew S., additional, Wentworth, David E., additional, and Barnes, John R., additional

Published
2019
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21. Author Correction: Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants

Author

Welch, Nicole L., Zhu, Meilin, Hua, Catherine, Weller, Juliane, Mirhashemi, Marzieh Ezzaty, Nguyen, Tien G., Mantena, Sreekar, Bauer, Matthew R., Shaw, Bennett M., Ackerman, Cheri M., Thakku, Sri Gowtham, Tse, Megan W., Kehe, Jared, Uwera, Marie-Martine, Eversley, Jacqueline S., Bielwaski, Derek A., McGrath, Graham, Braidt, Joseph, Johnson, Jeremy, Cerrato, Felecia, Moreno, Gage K., Krasilnikova, Lydia A., Petros, Brittany A., Gionet, Gabrielle L., King, Ewa, Huard, Richard C., Jalbert, Samantha K., Cleary, Michael L., Fitzgerald, Nicholas A., Gabriel, Stacey B., Gallagher, Glen R., Smole, Sandra C., Madoff, Lawrence C., Brown, Catherine M., Keller, Matthew W., Wilson, Malania M., Kirby, Marie K., Barnes, John R., Park, Daniel J., Siddle, Katherine J., Happi, Christian T., Hung, Deborah T., Springer, Michael, MacInnis, Bronwyn L., Lemieux, Jacob E., Rosenberg, Eric, Branda, John A., Blainey, Paul C., Sabeti, Pardis C., and Myhrvold, Cameron

Published
2024
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22. Direct RNA Sequencing of the Complete Influenza A Virus Genome

Author

Keller, Matthew W., primary, Rambo-Martin, Benjamin L., additional, Wilson, Malania M., additional, Ridenour, Callie A., additional, Shepard, Samuel S., additional, Stark, Thomas J., additional, Neuhaus, Elizabeth B., additional, Dugan, Vivien G., additional, Wentworth, David E., additional, and Barnes, John R., additional

Published
2018
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30. Bioprocessing analysis of Pyrococcus furiosus strains engineered for CO2-based 3-hydroxypropionate production.

Author

Hawkins, Aaron B., Lian, Hong, Zeldes, Benjamin M., Loder, Andrew J., Lipscomb, Gina L., Schut, Gerrit J., Keller, Matthew W., Adams, Michael W.W., and Kelly, Robert M.

Abstract

ABSTRACT Metabolically engineered strains of the hyperthermophile Pyrococcus furiosus (Topt 95-100°C), designed to produce 3-hydroxypropionate (3HP) from maltose and CO2 using enzymes from the Metallosphaera sedula (Topt 73°C) carbon fixation cycle, were examined with respect to the impact of heterologous gene expression on metabolic activity, fitness at optimal and sub-optimal temperatures, gas-liquid mass transfer in gas-intensive bioreactors, and potential bottlenecks arising from product formation. Transcriptomic comparisons of wild-type P. furiosus, a genetically-tractable, naturally-competent mutant (COM1), and COM1-based strains engineered for 3HP production revealed numerous differences after being shifted from 95°C to 72°C, where product formation catalyzed by the heterologously-produced M. sedula enzymes occurred. At 72°C, significantly higher levels of metabolic activity and a stress response were evident in 3HP-forming strains compared to the non-producing parent strain (COM1). Gas-liquid mass transfer limitations were apparent, given that 3HP titers and volumetric productivity in stirred bioreactors could be increased over 10-fold by increased agitation and higher CO2 sparging rates, from 18 mg/L to 276 mg/L and from 0.7 mg/L/h to 11 mg/L/h, respectively. 3HP formation triggered transcription of genes for protein stabilization and turnover, RNA degradation, and reactive oxygen species detoxification. The results here support the prospects of using thermally diverse sources of pathways and enzymes in metabolically engineered strains designed for product formation at sub-optimal growth temperatures. Biotechnol. Bioeng. 2015;112: 1533-1543. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Published
2015
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31. SARS-CoV-2 spike D614G change enhances replication and transmission

Author

Zhou, Bin, Tran, Thi Nhu Thao, Hoffmann, Donata, Taddeo, Adriano, Ebert, Nadine, Labroussaa, Fabien, Pohlmann, Anne, King, Jacqueline, Steiner, Silvio, Kelly, Jenna N., Portmann, Jasmine, Halwe, Nico Joel, Ulrich, Lorenz, Trüeb, Bettina Salome, Fan, Xiaoyu, Hoffmann, Bernd, Wang, Li, Thomann, Lisa, Lin, Xudong, Stalder, Hanspeter, Pozzi, Berta, De Brot, Simone, Jiang, Nannan, Cui, Dan, Hossain, Jaber, Wilson, Malania M., Keller, Matthew W., Stark, Thomas J., Barnes, John R., Dijkman, Ronald, Jores, Jörg, Benarafa, Charaf, Wentworth, David E., Thiel, Volker, and Beer, Martin

Subjects
630 Agriculture, 570 Life sciences, biology, 610 Medicine & health, 3. Good health
Abstract

During the evolution of SARS-CoV-2 in humans, a D614G substitution in the spike glycoprotein (S) has emerged; virus containing this substitution has become the predominant circulating variant in the COVID-19 pandemic1. However, whether the increasing prevalence of this variant reflects a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains unknown. Here we use isogenic SARS-CoV-2 variants to demonstrate that the variant that contains S(D614G) has enhanced binding to the human cell-surface receptor angiotensin-converting enzyme 2 (ACE2), increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a human ACE2 knock-in mouse model, and markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Our data show that the D614G substitution in S results in subtle increases in binding and replication in vitro, and provides a real competitive advantage in vivo-particularly during the transmission bottleneck. Our data therefore provide an explanation for the global predominance of the variant that contains S(D614G) among the SARS-CoV-2 viruses that are currently circulating.

32. Targeted amplification and genetic sequencing of the severe acute respiratory syndrome coronavirus 2 surface glycoprotein.

Author

Keller MW, Keong LM, Rambo-Martin BL, Hassell N, Lacek KA, Wilson MM, Kirby MK, Liddell J, Owuor DC, Sheth M, Madden J, Lee JS, Kondor RJ, Wentworth DE, and Barnes JR

Subjects
Humans, SARS-CoV-2 genetics, Pandemics, Membrane Glycoproteins, COVID-19 epidemiology, Vaccines
Abstract

Importance: The COVID-19 pandemic was accompanied by an unprecedented surveillance effort. The resulting data were and will continue to be critical for surveillance and control of SARS-CoV-2. However, some genomic surveillance methods experienced challenges as the virus evolved, resulting in incomplete and poor quality data. Complete and quality coverage, especially of the S-gene, is important for supporting the selection of vaccine candidates. As such, we developed a robust method to target the S-gene for amplification and sequencing. By focusing on the S-gene and imposing strict coverage and quality metrics, we hope to increase the quality of surveillance data for this continually evolving gene. Our technique is currently being deployed globally to partner laboratories, and public health representatives from 79 countries have received hands-on training and support. Expanding access to quality surveillance methods will undoubtedly lead to earlier detection of novel variants and better inform vaccine strain selection., Competing Interests: The authors declare no conflict of interest.

Published
2024
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33. Genomic Surveillance for SARS-CoV-2 Variants: Predominance of the Delta (B.1.617.2) and Omicron (B.1.1.529) Variants - United States, June 2021-January 2022.

Author

Lambrou AS, Shirk P, Steele MK, Paul P, Paden CR, Cadwell B, Reese HE, Aoki Y, Hassell N, Zheng XY, Talarico S, Chen JC, Oberste MS, Batra D, McMullan LK, Halpin AL, Galloway SE, MacCannell DR, Kondor R, Barnes J, MacNeil A, Silk BJ, Dugan VG, Scobie HM, Wentworth DE, Caravas J, Kovacs NA, Gerhart JG, Jia Ng H, Beck A, Chau R, Cintron R, Cook PW, Gulvik CA, Howard D, Jang Y, Knipe K, Lacek KA, Moser KA, Paskey AC, Rambo-Martin BL, Nagilla RR, Retchless AC, Schmerer MW, Seby S, Shepard SS, Stanton RA, Stark TJ, Uehara A, Unoarumhi Y, Bentz ML, Burgin A, Burroughs M, Davis ML, Keller MW, Keong LM, Le SS, Lee JS, Madden Jr JC, Nobles S, Owuor DC, Padilla J, Sheth M, and Wilson MM

Subjects
Centers for Disease Control and Prevention, U.S., Genomics, Humans, Prevalence, Public Health Surveillance methods, United States epidemiology, COVID-19 epidemiology, COVID-19 virology, SARS-CoV-2 genetics
Abstract

Genomic surveillance is a critical tool for tracking emerging variants of SARS-CoV-2 (the virus that causes COVID-19), which can exhibit characteristics that potentially affect public health and clinical interventions, including increased transmissibility, illness severity, and capacity for immune escape. During June 2021-January 2022, CDC expanded genomic surveillance data sources to incorporate sequence data from public repositories to produce weighted estimates of variant proportions at the jurisdiction level and refined analytic methods to enhance the timeliness and accuracy of national and regional variant proportion estimates. These changes also allowed for more comprehensive variant proportion estimation at the jurisdictional level (i.e., U.S. state, district, territory, and freely associated state). The data in this report are a summary of findings of recent proportions of circulating variants that are updated weekly on CDC's COVID Data Tracker website to enable timely public health action. † The SARS-CoV-2 Delta (B.1.617.2 and AY sublineages) variant rose from 1% to >50% of viral lineages circulating nationally during 8 weeks, from May 1-June 26, 2021. Delta-associated infections remained predominant until being rapidly overtaken by infections associated with the Omicron (B.1.1.529 and BA sublineages) variant in December 2021, when Omicron increased from 1% to >50% of circulating viral lineages during a 2-week period. As of the week ending January 22, 2022, Omicron was estimated to account for 99.2% (95% CI = 99.0%-99.5%) of SARS-CoV-2 infections nationwide, and Delta for 0.7% (95% CI = 0.5%-1.0%). The dynamic landscape of SARS-CoV-2 variants in 2021, including Delta- and Omicron-driven resurgences of SARS-CoV-2 transmission across the United States, underscores the importance of robust genomic surveillance efforts to inform public health planning and practice., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Published
2022
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34. Bioprocessing analysis of Pyrococcus furiosus strains engineered for CO₂-based 3-hydroxypropionate production.

Author

Hawkins AB, Lian H, Zeldes BM, Loder AJ, Lipscomb GL, Schut GJ, Keller MW, Adams MW, and Kelly RM

Subjects
Bioreactors microbiology, Gene Expression Profiling, Hot Temperature, Lactic Acid metabolism, Maltose metabolism, Pyrococcus furiosus radiation effects, Sulfolobaceae genetics, Carbon Dioxide metabolism, Lactic Acid analogs & derivatives, Metabolic Engineering methods, Metabolic Networks and Pathways genetics, Pyrococcus furiosus genetics, Pyrococcus furiosus metabolism
Abstract

Metabolically engineered strains of the hyperthermophile Pyrococcus furiosus (T(opt) 95-100°C), designed to produce 3-hydroxypropionate (3HP) from maltose and CO2 using enzymes from the Metallosphaera sedula (T(opt) 73°C) carbon fixation cycle, were examined with respect to the impact of heterologous gene expression on metabolic activity, fitness at optimal and sub-optimal temperatures, gas-liquid mass transfer in gas-intensive bioreactors, and potential bottlenecks arising from product formation. Transcriptomic comparisons of wild-type P. furiosus, a genetically-tractable, naturally-competent mutant (COM1), and COM1-based strains engineered for 3HP production revealed numerous differences after being shifted from 95°C to 72°C, where product formation catalyzed by the heterologously-produced M. sedula enzymes occurred. At 72°C, significantly higher levels of metabolic activity and a stress response were evident in 3HP-forming strains compared to the non-producing parent strain (COM1). Gas-liquid mass transfer limitations were apparent, given that 3HP titers and volumetric productivity in stirred bioreactors could be increased over 10-fold by increased agitation and higher CO2 sparging rates, from 18 mg/L to 276 mg/L and from 0.7 mg/L/h to 11 mg/L/h, respectively. 3HP formation triggered transcription of genes for protein stabilization and turnover, RNA degradation, and reactive oxygen species detoxification. The results here support the prospects of using thermally diverse sources of pathways and enzymes in metabolically engineered strains designed for product formation at sub-optimal growth temperatures., (© 2015 Wiley Periodicals, Inc.)

Published
2015
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