Sucrose-driven carbon redox rebalancing eliminates the Crabtree effect and boosts energy metabolism in yeast
Journal article, 2025
Saccharomyces cerevisiae primarily generates energy through glycolysis and respiration. However, the manifestation of the Crabtree effect results in substantial carbon loss and energy inefficiency, which significantly diminishes product yield and escalates substrate costs in microbial cell factories. To address this challenge, we introduce the sucrose phosphorolysis pathway and delete the phosphoglucose isomerase gene PGI1, effectively decoupling glycolysis from respiration and facilitating the metabolic transition of yeast to a Crabtree-negative state. Additionally, a synthetic energy system is engineered to regulate the NADH/NAD+ ratio, ensuring sufficient ATP supply and maintaining redox balance for optimal growth. The reprogrammed yeast strain exhibits significantly higher yields of various non-ethanol compounds, with lactic acid and 3-hydroxypropionic acid production increasing by 8- to 11-fold comparing to the conventional Crabtree-positive strain. This study describes an approach for overcoming the Crabtree effect in yeast, substantially improving energy metabolism, carbon recovery, and product yields.
Author
Zhiqiang Xiao
Hunan University
Hunan Academy of Agricultural Sciences
Hunan Agricultural Product Processing Institute
Yifei Zhao
Hunan University
Hunan Agricultural Product Processing Institute
Hunan Academy of Agricultural Sciences
Yongtong Wang
Hunan Academy of Agricultural Sciences
Hunan University
Hunan Agricultural Product Processing Institute
Xinjia Tan
Hunan Agricultural Product Processing Institute
Hunan University
Hunan Academy of Agricultural Sciences
Lian Wang
Tianjin University
Jiwei Mao
Chalmers, Life Sciences, Systems and Synthetic Biology
Siqi Zhang
Hunan Academy of Agricultural Sciences
Hunan Agricultural Product Processing Institute
Hunan University
Qiyuan Lu
Hunan Agricultural Product Processing Institute
Hunan Academy of Agricultural Sciences
Hunan University
Fanglin Hu
Hunan Agricultural Product Processing Institute
Hunan Academy of Agricultural Sciences
Hunan University
Shasha Zuo
Hunan Academy of Agricultural Sciences
Hunan Agricultural Product Processing Institute
Hunan University
Juan Liu
Hunan Academy of Agricultural Sciences
Hunan Agricultural Product Processing Institute
Yang Shan
Hunan University
Hunan Agricultural Product Processing Institute
Hunan Academy of Agricultural Sciences
Nature Communications
2041-1723 (ISSN) 20411723 (eISSN)
Vol. 16 1 5211Subject Categories (SSIF 2025)
Molecular Biology
Energy Systems
Other Industrial Biotechnology
DOI
10.1038/s41467-025-60578-8