Disruption of malate:quinone oxidoreductase increases L-lysine production by Corynebacterium glutamicum.
Genomic analysis of a classically derived L-lysine-producing mutant, Corynebacterium glutamicum B-6, identified a nonsense mutation in the mqo gene, which encodes malate:quinone oxidoreductase (MQO). The effect of mqo disruption on L-lysine production was investigated in a defined L-lysine producer, C. glutamicum AHP-3, showing approximately 18% increased production. To explore the underlying mechanisms of the increase, the mqo-disrupted strain was analyzed from the viewpoints of redox balance, activities of membrane-bound dehydrogenases, and transcriptome. The intracellular [NADH]/[NAD] ratio in the strain remained unchanged. Also, there were no significant differences in the activities of the membrane-bound dehydrogenases examined. However, transcriptome analysis showed that some TCA cycle genes, such as acn, sucC, and sucD, were down-regulated in the strain. These results suggest that the loss of MQO activity down-regulates the flux of the TCA cycle to maintain the redox balance and results in redirection of oxaloacetate into L-lysine biosynthesis.
Mitsuhashi
Satoshi
S
Biofrontier Laboratories, Kyowa Hakko Kogyo Co., Ltd. Asahi-machi, Machida. Tokyo, Japan.
Hayashi
Mikiro
M
Ohnishi
Junko
J
Ikeda
Masato
M
D048230:Corynebacterium glutamicum / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D008239:Lysine / Q000096:biosynthesis*; D010088:Oxidoreductases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
D010088:Oxidoreductases; C471971:malate dehydrogenase, FAD-dependent; D008239:Lysine