Escherichia coli segments its controls on carbon‐dependent gene expression into global and specific regulations

• Published in: Microbial biotechnology Vol. 14; no. 3; pp. 1084 - 1106
• Main Authors: Pan, Qing, Li, Zongjin, Ju, Xian, Hou, Chaofan, Xiao, Yunzhu, Shi, Ruoping, Fu, Chunxiang, Danchin, Antoine, You, Conghui
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.05.2021; John Wiley and Sons Inc; Wiley
• Subjects: Bacterial Proteins - genetics; Carbon; Carbon - metabolism; Carbon sources; E coli; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Gene Expression; Gene Expression Regulation, Bacterial; Genes; Glucose; Glycolysis; Growth rate; Metabolic pathways; Metabolism; Phosphotransferase; Proteins; Repressor Proteins - metabolism; Substrates; Sugar
• ISSN: 1751-7915; 1751-7915
• DOI: 10.1111/1751-7915.13776

Summary How bacteria adjust gene expression to cope with variable environments remains open to question. Here, we investigated the way global gene expression changes in E. coli correlated with the metabolism of seven carbon substrates chosen to trigger a large panel of metabolic pathways. Coarse‐grained analysis of gene co‐expression identified a novel regulation pattern: we established that the gene expression trend following immediately the reduction of growth rate (GR) was correlated to its initial expression level. Subsequent fine‐grained analysis of co‐expression demonstrated that the Crp regulator, coupled with a change in GR, governed the response of most GR‐dependent genes. By contrast, the Cra, Mlc and Fur regulators governed the expression of genes responding to non‐glycolytic substrates, glycolytic substrates or phosphotransferase system transported sugars following an idiosyncratic way. This work allowed us to expand additional genes in the panel of gene complement regulated by each regulator and to elucidate the regulatory functions of each regulator comprehensively. Interestingly, the bulk of genes controlled by Cra and Mlc were, respectively, co‐regulated by Crp‐ or GR‐related effect and our quantitative analysis showed that each factor took turns to work as the primary one or contributed equally depending on the conditions. Here, we deciphered the global regulatory strategy that E. coli applies to cope with the metabolism of an array of carbon substrates with distinctive features. In this process, we disentangled the individual and coordinated contributions of various control responses (Crp, Cra, Mlc, Fur and GR‐related effect) and identified a novel rule of regulation. The comprehensive knowledge of gene regulation revealed here makes E. coli an ideal organism for biotech fermentation.