Uncoupling growth and succinic acid production in an industrial Saccharomyces cerevisiae strain

Yaya Liu, Osman Esen, Jack T. Pronk, Walter M. van Gulik*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

9 Citations (Scopus)
24 Downloads (Pure)


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, that is, 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 the biomass-specific SA production rate and glucose consumption rate indicated the 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.

Original languageEnglish
Pages (from-to)1576-1586
Number of pages11
JournalBiotechnology and Bioengineering
Issue number4
Publication statusPublished - 2021


  • high CO
  • low pH
  • near-zero growth
  • retentostat
  • succinic acid


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