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Genetic-Metabolic Coupling for Targeted Metabolic Engineering.
- Source :
-
Cell reports [Cell Rep] 2017 Aug 01; Vol. 20 (5), pp. 1029-1037. - Publication Year :
- 2017
-
Abstract
- Production of chemicals in microbes often employs potent biosynthetic enzymes, which can interact with the microbial native metabolism to affect cell fitness and product yield. However, production optimization largely relies on data collected from wild-type strains in the absence of metabolic perturbations, thus limiting their relevance to specific conditions. Here, we address this issue by coupling cell fitness to the production of thiamine diphosphate in Escherichia coli using a synthetic RNA biosensor. We use this strategy to interrogate a library of transposon mutants and elucidate the native gene network influencing both cell fitness and thiamine production. Ultimately, we identify effectors of the OxyR-Fur stress response that limit thiamine biosynthesis via alternative regulation of iron storage and Fe-S cluster inclusion in enzymes. This study presents a new approach for the reliable high-throughput identification of genetic targets of both known and unknown function that are directly relevant to a specific biosynthetic process.<br /> (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Bacterial Proteins genetics
Bacterial Proteins metabolism
Escherichia coli genetics
Escherichia coli metabolism
Escherichia coli Proteins genetics
Escherichia coli Proteins metabolism
Metabolic Engineering
Repressor Proteins genetics
Repressor Proteins metabolism
Thiamine Pyrophosphate biosynthesis
Thiamine Pyrophosphate genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 20
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 28768189
- Full Text :
- https://doi.org/10.1016/j.celrep.2017.07.015