Sucrose-driven carbon redox rebalancing eliminates the Crabtree effect and boosts energy metabolism in yeast

文献类型： 外文期刊

第一作者： Xiao, Zhiqiang

作者： Xiao, Zhiqiang;Zhao, Yifei;Wang, Yongtong;Tan, Xinjia;Zhang, Siqi;Lu, Qiyuan;Hu, Fanglin;Zuo, Shasha;Shan, Yang;Xiao, Zhiqiang;Zhao, Yifei;Wang, Yongtong;Tan, Xinjia;Zhang, Siqi;Lu, Qiyuan;Hu, Fanglin;Zuo, Shasha;Liu, Juan;Shan, Yang;Xiao, Zhiqiang;Zhao, Yifei;Wang, Yongtong;Tan, Xinjia;Zhang, Siqi;Lu, Qiyuan;Hu, Fanglin;Zuo, Shasha;Liu, Juan;Shan, Yang;Wang, Lian;Wang, Lian;Mao, Jiwei

作者机构：

期刊名称：NATURE COMMUNICATIONS （ 影响因子：15.7； 五年影响因子：17.2 ）

ISSN：

年卷期： 2025 年 16 卷 1 期

页码：

收录情况： SCI

摘要： 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.

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