RRC ID 66215
Author Cotton CA, Bernhardsgrütter I, He H, Burgener S, Schulz L, Paczia N, Dronsella B, Erban A, Toman S, Dempfle M, De Maria A, Kopka J, Lindner SN, Erb TJ, Bar-Even A.
Title Underground isoleucine biosynthesis pathways in E. coli.
Journal Elife
Abstract The promiscuous activities of enzymes provide fertile ground for the evolution of new metabolic pathways. Here, we systematically explore the ability of E. coli to harness underground metabolism to compensate for the deletion of an essential biosynthetic pathway. By deleting all threonine deaminases, we generated a strain in which isoleucine biosynthesis was interrupted at the level of 2-ketobutyrate. Incubation of this strain under aerobic conditions resulted in the emergence of a novel 2-ketobutyrate biosynthesis pathway based upon the promiscuous cleavage of O-succinyl-L-homoserine by cystathionine γ-synthase (MetB). Under anaerobic conditions, pyruvate formate-lyase enabled 2-ketobutyrate biosynthesis from propionyl-CoA and formate. Surprisingly, we found this anaerobic route to provide a substantial fraction of isoleucine in a wild-type strain when propionate is available in the medium. This study demonstrates the selective advantage underground metabolism offers, providing metabolic redundancy and flexibility which allow for the best use of environmental carbon sources.
Volume 9
Published 2020-8-24
DOI 10.7554/eLife.54207
PII 54207
PMID 32831171
PMC PMC7476758
MeSH Butyrates / metabolism* Carbon-Oxygen Lyases / metabolism* Escherichia coli / genetics Escherichia coli / metabolism* Gene Deletion* Homoserine / analogs & derivatives* Homoserine / metabolism Isoleucine / metabolism* Metabolic Networks and Pathways
IF 7.08
Prokaryotes E. coli MG1655