Acetate is a beneficial nutrient for E. coli at low glycolytic flux

被引:7
|
作者
Millard, Pierre [1 ,2 ]
Gosselin-Monplaisir, Thomas [1 ]
Uttenweiler-Joseph, Sandrine [1 ]
Enjalbert, Brice [1 ]
机构
[1] Univ Toulouse, TBI, CNRS, INRAE,INSA, Toulouse, France
[2] Natl Infrastruct Metabol & Fluxom, MetaToul MetaboHUB, Toulouse, France
来源
EMBO JOURNAL | 2023年 / 42卷 / 15期
关键词
acetate; kinetic model; metabolism; regulation; robustness; ESCHERICHIA-COLI; ACETIC-ACID; METABOLISM; FERMENTATION; INHIBITION; GLUCOSE; GROWTH; BACTERIA; LACTATE; O157H7;
D O I
10.15252/embj.2022113079
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Acetate, a major by-product of glycolytic metabolism in Escherichia coli and many other microorganisms, has long been considered a toxic waste compound that inhibits microbial growth. This counterproductive auto-inhibition represents a major problem in biotechnology and has puzzled the scientific community for decades. Recent studies have however revealed that acetate is also a co-substrate of glycolytic nutrients and a global regulator of E. coli metabolism and physiology. Here, we used a systems biology strategy to investigate the mutual regulation of glycolytic and acetate metabolism in E. coli. Computational and experimental analyses demonstrate that decreasing the glycolytic flux enhances co-utilization of acetate with glucose. Acetate metabolism thus compensates for the reduction in glycolytic flux and eventually buffers carbon uptake so that acetate, rather than being toxic, actually enhances E. coli growth under these conditions. We validated this mechanism using three orthogonal strategies: chemical inhibition of glucose uptake, glycolytic mutant strains, and alternative substrates with a natively low glycolytic flux. In summary, acetate makes E. coli more robust to glycolytic perturbations and is a valuable nutrient, with a beneficial effect on microbial growth.
引用
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页数:12
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