Adaptive laboratory evolution recruits the promiscuity of succinate semialdehyde dehydrogenase to repair different metabolic deficiencies

• 全文链接

适应性实验室进化招募了琥珀酸半醛脱氢酶的杂乱性来修复不同的代谢缺陷

关键词：

来源：

NATURE COMMUNICATIONS

全文链接：

//agri.nais.net.cn/topic/downloadFile/f5e15e5c-a9bb-47ef-8ae3-2637fbcbaf8c

来源地址：

https://www.nature.com/articles/s41467-024-53156-x

资源所属：

饲料用酶工程

类型：

学术文献

语种：

中文

原文发布日期：

2024-10-15

摘要：

Promiscuous enzymes often serve as the starting point for the evolution of novel functions. Yet, the extent to which the promiscuity of an individual enzyme can be harnessed several times independently for different purposes during evolution is poorly reported. Here, we present a case study illustrating how NAD(P)+-dependent succinate semialdehyde dehydrogenase of Escherichia coli (Sad) is independently recruited through various evolutionary mechanisms for distinct metabolic demands, in particular vitamin biosynthesis and central carbon metabolism. Using adaptive laboratory evolution (ALE), we show that Sad can substitute for the roles of erythrose 4-phosphate dehydrogenase in pyridoxal 5’-phosphate (PLP) biosynthesis and glyceraldehyde 3-phosphate dehydrogenase in glycolysis. To recruit Sad for PLP biosynthesis and glycolysis, ALE employs various mechanisms, including active site mutation, copy number amplification, and (de)regulation of gene expression. Our study traces down these different evolutionary trajectories, reports on the surprising active site plasticity of Sad, identifies regulatory links in amino acid metabolism, and highlights the potential of an ordinary enzyme as innovation reservoir for evolution.