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Uncoupling growth and succinic acid production in an industrial Saccharomyces cerevisiae strain
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  • Yaya Liu,
  • Osman Esen,
  • Jack T. Pronk,
  • Walter Martin van Gulik
Yaya Liu
TU Delft

Corresponding Author:[email protected]

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Osman Esen
TU Delft
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Jack T. Pronk
TU Delft
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Walter Martin van Gulik
TU Delft
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This study explores the relation between biomass-specific succinic acid (SA) production rate and specific growth rate of an engineered industrial strain of Saccharomyces cerevisiae, with the aim to investigate the extent to which growth and product formation can be uncoupled. Ammonium-limited aerobic chemostat and retentostat cultures were grown at different specific growth rates under industrially relevant conditions, i.e., at a culture pH of 3 and with sparging of a 1:1 CO2-air mixture. Biomass-specific SA production rates decreased asymptotically with decreasing growth rate. At near-zero growth rates, the engineered strain maintained a stable biomass-specific SA production rate for over 500 h, with a SA yield on glucose of 0.61 mol.mol-1. These results demonstrate that uncoupling of growth and SA production could indeed be achieved. A linear relation between biomass-specific SA production rate and glucose consumption rate indicated a coupling of SA production rate and the flux through primary metabolism. The low culture pH resulted in an increased death rate, which was lowest at near-zero growth rates. Nevertheless, a significant amount of non-viable biomass accumulated in the retentostat cultures, thus underlining the importance of improving low-pH tolerance in further strain development for industrial SA production with S. cerevisiae.
15 Jun 2020Submitted to Biotechnology and Bioengineering
16 Jun 2020Submission Checks Completed
16 Jun 2020Assigned to Editor
29 Jun 2020Reviewer(s) Assigned
07 Aug 2020Review(s) Completed, Editorial Evaluation Pending
07 Aug 2020Editorial Decision: Revise Major
14 Sep 20201st Revision Received
15 Sep 2020Assigned to Editor
15 Sep 2020Submission Checks Completed
26 Sep 2020Reviewer(s) Assigned
01 Nov 2020Editorial Decision: Revise Minor
01 Nov 2020Review(s) Completed, Editorial Evaluation Pending
13 Dec 20202nd Revision Received
14 Dec 2020Assigned to Editor
14 Dec 2020Submission Checks Completed
29 Dec 2020Review(s) Completed, Editorial Evaluation Pending
29 Dec 2020Editorial Decision: Accept
Apr 2021Published in Biotechnology and Bioengineering volume 118 issue 4 on pages 1557-1567. 10.1002/bit.27672