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Energy-translation coupling limits anaerobic yeast growth
Yongbo Wang1, Yu Huang1, Yazhi Liu1
1State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
Nature Communications
|June 12, 2026
Summary
Yeast anaerobic growth is limited by energy and protein synthesis, not just sugar intake. Engineering these pathways boosts growth rates under various nutrient limitations.
Area of Science:
- Biochemistry
- Metabolic Engineering
- Microbiology
Background:
- Understanding nutrient limitations is key to defining yeast physiological limits.
- Anaerobic metabolism in Saccharomyces cerevisiae is crucial for industrial applications.
Purpose of the Study:
- To investigate how nutrient limitations (carbon, nitrogen, phosphorus) shape yeast anaerobic metabolism.
- To identify the specific bottlenecks constraining maximal anaerobic growth rate.
- To engineer yeast for enhanced anaerobic growth.
Main Methods:
- Chemostat cultivation under strictly anaerobic conditions.
- Multi-omic profiling (genomics, transcriptomics, proteomics, metabolomics).
- Targeted metabolic engineering and strain development.
Main Results:
- Yeast maintains a conserved maximum glucose uptake under C, N, and P limitation.
- Distinct bottlenecks limit growth: ATP insufficiency (C, P limitation) and aminoacyl-tRNA synthetase scarcity (N limitation).
- Engineered strains (VMA3, WRS1) showed significant increases in maximal anaerobic growth rates (27.2%–52.5%).
Conclusions:
- Energy-translation coupling is the central determinant of yeast anaerobic growth limits.
- Nutrient-specific regulatory networks and proteomic reallocation are key responses to stress.
- A "push-pull" engineering strategy effectively enhances anaerobic growth, providing a framework for strain development.
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