Alterations in the transcription factors GntR1 and RamA enhance the growth and central metabolism of Corynebacterium glutamicum

Metabolic Engineering
Zhihao WangPeter Ruhdal Jensen

Abstract

Evolution, i.e. the change in heritable characteristics of biological populations over successive generations, has created the diversity of life that exists today. In this study we have harnessed evolution to create faster growing mutants of Corynebacterium glutamicum, i.e. to debottleneck growth rate of this highly important industrial workhorse. After approximately 1500 generations of Adaptive Laboratory Evolution (ALE) in defined minimal medium with glucose, we obtained faster growing mutants with specific growth rate as high as 0.64 h-1 as compared with 0.45 h-1 for the wild type, and this 42% improvement is the highest reported for C. glutamicum to date. By genome resequencing and inverse metabolic engineering, we were able to pinpoint two mutations contributing to most of the growth improvement, and these resided in the transcriptional regulators GntR1 (gntR1-E70K) and RamA (ramA-A52V). We confirmed that the two mutations lead to alteration rather than elimination of function, and their introduction in the wild-type background resulted in a specific growth rate of 0.62 h-1. The glycolytic and pentose phosphate pathway fluxes had both increased significantly, and a transcriptomic analyses supported this to be associated wi...Continue Reading

Citations

Mar 31, 2019·Biotechnology Journal·Roberto G StellaJulia Frunzke
Jun 11, 2020·Biomolecules·Egle ValancieneNaglis Malys
Feb 16, 2019·Phytotherapy Research : PTR·Hongnan ZhengJianbo Wang
Nov 15, 2018·Frontiers in Microbiology·Fernando Pérez-GarcíaVolker F Wendisch
May 28, 2019·Frontiers in Microbiology·Thorsten HaasRalf Takors
Nov 13, 2020·Frontiers in Bioengineering and Biotechnology·Michaela GrafRalf Takors
May 12, 2021·Microbial Cell Factories·Carina PrellVolker F Wendisch
Apr 4, 2019·Metabolic Engineering·Volker F Wendisch

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