Engineered strains of Saccharomyces cerevisiae are used for industrial production of succinic acid. Optimal process conditions for dicarboxylic-acid yield and recovery include slow growth, low pH, and high CO₂ . To quantify and understand how these process parameters affect yeast physiology, this study investigates individual and combined impacts of low pH (3.0) and high CO₂ (50%) on slow-growing chemostat and retentostat cultures of the reference strain S. cerevisiae CEN.PK113-7D. Combined exposure to low pH and high CO₂ led to increased maintenance-energy requirements and death rates in aerobic, glucose-limited cultures. Further experiments showed that these effects were predominantly caused by low pH. Growth under ammonium-limited, energy-excess conditions did not aggravate or ameliorate these adverse impacts. Despite the absence of a synergistic effect of low pH and high CO₂ on physiology, high CO₂ strongly affected genome-wide transcriptional responses to low pH. Interference of high CO₂ with low-pH signaling is consistent with low-pH and high-CO₂ signals being relayed via common (MAPK) signaling pathways, notably the cell wall integrity, high-osmolarity glycerol, and calcineurin pathways. This study highlights the need to further increase robustness of cell factories to low pH for carboxylic-acid production, even in organisms that are already applied at industrial scale.

• PMID: 31654410
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Journal Article | Research Support, Non-U.S. Gov't

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Hakkaart X, Liu Y, Hulst M, El Masoudi A, Peuscher E, Pronk J, van Gulik W, Daran-Lapujade P

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