Mitsuhashi Satoshi, Hayashi Mikiro, Ohnishi Junko, Ikeda Masato
Biofrontier Laboratories, Kyowa Hakko Kogyo Co., Ltd. Asahi-machi, Machida. Tokyo, Japan.
Biosci Biotechnol Biochem. 2006 Nov;70(11):2803-6. doi: 10.1271/bbb.60298. Epub 2006 Nov 7.
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.
对一株经典诱变产生的产L-赖氨酸突变体谷氨酸棒杆菌B-6进行基因组分析，发现mqo基因存在无义突变，该基因编码苹果酸：醌氧化还原酶（MQO）。在一株特定的L-赖氨酸生产菌谷氨酸棒杆菌AHP-3中研究了mqo基因破坏对L-赖氨酸生产的影响，结果显示产量提高了约18%。为探究产量增加的潜在机制，从氧化还原平衡、膜结合脱氢酶活性和转录组等方面对mqo基因破坏菌株进行了分析。该菌株细胞内的[NADH]/[NAD]比值保持不变。此外，所检测的膜结合脱氢酶活性也没有显著差异。然而，转录组分析表明，该菌株中一些三羧酸循环（TCA）基因，如acn、sucC和sucD，表达下调。这些结果表明，MQO活性的丧失下调了TCA循环通量以维持氧化还原平衡，并导致草酰乙酸重新导向L-赖氨酸生物合成。
