Acetate overflow metabolism regulates a major metabolic shift after glucose depletion in Escherichia coli

FEBS Letters

article

Tomohiro Shimada¹  Kohta Nakazawa¹  Tomoyuki Tachikawa¹  Natsumi Saito³  Tatsuya Niwa⁵  Hideki Taguchi⁵  Kan Tanaka¹ 

[1] Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology;School of Life Science and Technology, Tokyo Institute of Technology;Institute for Advanced Biosciences, Keio University;Department of Creative Engineering, Tsuruoka College, National Institute of Technology;Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology

关键词: 2-oxoglutarate dehydrogenase;    acetate overflow metabolism;    coenzyme A;    gluconeogenesis;    glucose depletion;    glycolysis;    pyruvate dehydrogenase;   

DOI  :  10.1002/1873-3468.14151

来源: John Wiley & Sons Ltd.

【 摘 要 】

Acetate overflow refers to the metabolism by which a large part of carbon incorporated as glucose into Escherichia coli cells is catabolized and excreted as acetate into the medium. We previously found that mutants for the acetate overflow pathway enzymes phosphoacetyltransferase (Pta) and acetate kinase (AckA) showed significant diauxic growth after glucose depletion in E. coli . Here, we analyzed the underlying mechanism in the pta mutant. Proteomic and other analyses revealed an increase in pyruvate dehydrogenase complex subunits and a decrease in glyoxylate shunt enzymes, which resulted from pyruvate accumulation. Since restoration of these enzyme levels by overexpressing PdhR (pyruvate-sensing transcription factor) or deleting iclR (gene encoding a pyruvate- and glyoxylate-sensing transcription factor) alleviated the growth lag of the pta mutant after glucose depletion, these changes were considered as the reason for the phenotype. Given the evidence for decreased coenzyme A (HS-CoA) levels in the pta mutant, the growth inhibition after glucose depletion was partly explained by limited availability of HS-CoA in the cell. The findings provide insights into the role of acetate overflow in metabolic regulation, which may be useful for biotechnological applications.

【 授权许可】

Unknown