丙二酰辅酶A
生物合成
生物化学
生物生产
代谢工程
羧化
乙酰辅酶A
柠檬酸合酶
柠檬酸循环
化学
生物
新陈代谢
酶
β氧化
催化作用
作者
Bo Liu,Yuwei Zhang,Qianqian Cui,Wu Sheng,Shuang‐Yan Tang,Yihua Chen,Yanhe Ma,Weifeng Liu,Yong Tao
标识
DOI:10.1101/2022.10.28.514148
摘要
Malonyl-CoA is a key metabolic intermediate for biosynthesis of diverse cellular molecules and natural products. Carboxylation of acetyl-CoA is almost the unique pathway for malonly-CoA biosynthesis. Biotechnological production of numerous value-added malonyl-CoA-derived chemicals require high intracellular supply of malonyl-CoA. However, because of the central role of acetyl-CoA in primary metabolism, it is difficult to develop flexible strategies to balance malonyl-CoA supply with other cellular metabolism. Here we find that there is a natural alternative malonyl-CoA-producing pathway, in which the key reaction is catalyzed by an α-keto acid dehydrogenase complex BkdFGH from Streptomyces avermitilis . This dehydrogenase complex could efficiently catalyze biosynthesis of malonyl-CoA from oxaloacetate in addition to recognizing its native substrate branched-chain α-keto acid. Oxaloacetate dehydrogenase (OADH) was shown to play important physiological roles during the regulation of biosynthesis of native malonyl-CoA-derived polyketides in Streptomyces . Furthermore, the oxlaocetate dehydrogenation reaction is thermodynamically superior to acetyl-CoA carboxylation and enable efficient bioproduction of diverse malonyl-CoA-derived chemicals in engineering Escherichia coli . This novel malonyl-CoA source thus has great potential in the biotechnological field.
科研通智能强力驱动
Strongly Powered by AbleSci AI