Sucrose-driven carbon redox rebalancing eliminates the Crabtree effect and boosts energy metabolism in yeast
Artikel i vetenskaplig tidskrift, 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.

Författare

Zhiqiang Xiao

Hunan Agricultural Product Processing Institute

Hunan Academy of Agricultural Sciences

Hunan University

Yifei Zhao

Hunan University

Hunan Academy of Agricultural Sciences

Hunan Agricultural Product Processing Institute

Yongtong Wang

Hunan Academy of Agricultural Sciences

Hunan Agricultural Product Processing Institute

Hunan University

Xinjia Tan

Hunan Agricultural Product Processing Institute

Hunan Academy of Agricultural Sciences

Hunan University

Lian Wang

Tianjin University

Jiwei Mao

Chalmers, Life sciences, Systembiologi

Siqi Zhang

Hunan University

Hunan Agricultural Product Processing Institute

Hunan Academy of Agricultural Sciences

Qiyuan Lu

Hunan Academy of Agricultural Sciences

Hunan Agricultural Product Processing Institute

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 Academy of Agricultural Sciences

Hunan Agricultural Product Processing Institute

Nature Communications

2041-1723 (ISSN) 20411723 (eISSN)

Vol. 16 1 5211

Ämneskategorier (SSIF 2025)

Molekylärbiologi

Energisystem

Annan industriell bioteknik

DOI

10.1038/s41467-025-60578-8

Mer information

Senast uppdaterat

2025-06-18