Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering, KAIST Institute for BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, KAIST, Daejeon, 34141, Republic of Korea.
Nat Commun. 2021 Jan 8;12(1):173. doi: 10.1038/s41467-020-20423-6.
Bio-based production of many chemicals is not yet possible due to the unknown biosynthetic pathways. Here, we report a strategy combining retrobiosynthesis and precursor selection step to design biosynthetic pathways for multiple short-chain primary amines (SCPAs) that have a wide range of applications in chemical industries. Using direct precursors of 15 target SCPAs determined by the above strategy, Streptomyces viridifaciens vlmD encoding valine decarboxylase is examined as a proof-of-concept promiscuous enzyme both in vitro and in vivo for generating SCPAs from their precursors. Escherichia coli expressing the heterologous vlmD produces 10 SCPAs by feeding their direct precursors. Furthermore, metabolically engineered E. coli strains are developed to produce representative SCPAs from glucose, including the one producing 10.67 g L of iso-butylamine by fed-batch culture. This study presents the strategy of systematically designing biosynthetic pathways for the production of a group of related chemicals as demonstrated by multiple SCPAs as examples.
由于未知的生物合成途径，许多化学物质的生物基生产目前还无法实现。在这里，我们报告了一种结合回溯合成和前体选择步骤的策略，用于设计多种短链伯胺（SCPA）的生物合成途径，这些伯胺在化学工业中有广泛的应用。使用通过上述策略确定的 15 种目标 SCPA 的直接前体，我们检验了来自其前体生成 SCPA 的天冬氨酸脱羧酶编码基因 vlmD 作为一种有前途的多功能酶的概念验证。表达异源 vlmD 的大肠杆菌通过喂养其直接前体产生了 10 种 SCPA。此外，还开发了代谢工程大肠杆菌菌株，以从葡萄糖生产代表性的 SCPA，包括通过分批补料培养生产 10.67 g/L 异丁胺的菌株。这项研究提出了一种系统设计生物合成途径的策略，以生产一组相关的化学物质，多个 SCPA 就是这一策略的例证。
