Understanding the high l-valine production in Corynebacterium glutamicum VWB-1 using transcriptomics and proteomics

Abstract

Toward the elucidation of the advanced mechanism of l-valine production by Corynebacterium glutamicum, a highly developed industrial strain VWB-1 was analyzed, employing the combination of transcriptomics and proteomics methods. The transcriptional level of 1155 genes and expression abundance of 96 proteins were changed significantly by the transcriptome and proteome comparison of VWB-1 and ATCC 13869. It was indicated that the key genes involved in the biosynthesis of l-valine, ilvBN, ilvC, ilvD, ilvE were up-regulated in VWB-1, which together made prominent contributions in improving the carbon flow towards l-valine. The l-leucine and l-isoleucine synthesis ability were weakened according to the down-regulation of leuB and ilvA. The up-regulation of the branched chain amino acid transporter genes brnFE promoted the l-valine secretion capability of VWB-1. The NADPH and ATP generation ability of VWB-1 were strengthened through the up-regulation of the genes involved in phosphate pentose pathway and TCA pathway. Pyruvate accumulation was achieved through the weakening of the l-lactate, acetate and l-alanine pathways. The up-regulation of the genes coding for elongation factors and ribosomal proteins were beneficial for l-valine synthesis in C. glutamicum. All information acquired were useful for the genome breeding of better industrial l-valine producing strains.

Metabolic fluxes for nutritional flexibility of Mycobacterium tuberculosis

“…The increase in biosynthesis of ILE during growth on CHL‐ACE is of interest as in other fungi and bacteria it has been shown that branched chain amino acid biosynthesis can also function as a mechanism to dissipate reductants (Shimizu et al, 2010; Zhang et al, 2018). Supported by the lipid profiling data here, it is thought that Mtb primarily uses lipids as an electron sink to maintain redox homeostasis when growing on highly reduced carbon sources such as cholesterol (Singh et al, 2009; Mavi et al, 2019).…”

Metabolic flux partitioning between the TCA cycle and glyoxylate shunt combined with a reversible methyl citrate cycle provide nutritional flexibility forMycobacterium tuberculosis

“…The increase in biosynthesis of ILE during growth on CHL-ACE is of interest as in other fungi and bacteria it has been shown that branched chain amino acid biosynthesis can also function as a mechanism to dissipate reductants (31–32) Supported by the lipid profiling data here it is thought that Mtb primarily uses lipids as an electron sink to maintain redox homeostasis when growing on highly reduced carbon sources such as cholesterol (24–26). However the role of amino acids as potential electron sinks has never been explored for Mtb.…”

Advances in metabolic engineering of Corynebacterium glutamicum to produce high-value active ingredients for food, feed, human health, and well-being

“…Producing strains are characterised by enhanced biosynthesis controlled by acetohydroxyacid synthase (AHAS, ilvN GE ), disrupted routes to undesired by-products (lactate, succinate), an amplified glycolytic pathway, and optimised redox balancing using an NAD-preferring mutant of acetohydroxyacid isomeroreductase (AHAIR, ilvC™) during production [57,60]. Transcriptomics and proteomics furthermore have revealed that up-regulation of the branched chain amino acid exporter genes brnFE promotes l-valine secretion capability [65], displaying a promising target for future metabolic engineering interventions [66]. Furthermore, it was also possible to generate l-leucine-producing strains of C. glutamicum characterised by the overexpression of feedback-resistant variants of the central enzyme 2-isopropylmalate synthase (IPMS, leuA) and a fine-tuned redistribution of precursor supply [57,67].…”