Modulation of the general stress response impacts protein expression, energy economy, and heterogeneity in virtually non-dividing yeast cultures.

In retentostat cultures of Saccharomyces cerevisiae at growth rates below 0.001 h⁻¹, deleting Msn2 and Msn4 increases heterogeneity and reduces viability while impairing energy efficiency.

• Why it matters: Extreme calorie restriction forces cells to balance survival with protein production, but how general stress-response regulators shape robustness and expression at near-zero growth is unclear.
• What they did: The study compared a reference strain (ScNTi001) and a Δ msn2 Δ msn4 mutant (ScNTm001) in retentostat conditions, then tracked activity of P_HSP12 and P_TEF1 and measured protein output using ymNeongreen.
• The result: P_HSP12 activity dropped sharply below 0.001 h⁻¹, while P_TEF1 sustained expression linked to glucose uptake; Δ msn2 Δ msn4 increased ymNeongreen-specific production rates by 70% but lowered overall product yields by 13%.

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