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Nat. Commun., Published 8 January 2021, 12, 173 | https://doi.org/10.1038/s41467-020-20423-6 Microbial production of multiple short-chain primary amines via retrobiosynthesis

Dong In Kim^1,2,5, Tong Un Chae^1,2,5, Hyun Uk Kim^2,3,4,5, Woo Dae Jang^1,2 & Sang Yup Lee^1,2,4,*

¹Metabolic 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.
²Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, KAIST, Daejeon 34141, Republic of Korea.
³Systems Biology and Medicine Laboratory, Department of Chemical and Biomolecular Engineering, KAIST, Daejeon 34141, Republic of Korea.
⁴KAIST Institute for Artificial Intelligence, BioProcess Engineering Research Center and BioInformatics Research Center, KAIST, Daejeon 34141, Republic of Korea.

⁵These authors contributed equally: Dong In Kim, Tong Un Chae, Hyun Uk Kim.

^*Corresponding author

Abstract

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⁻¹ 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.

논문정보

형식Research article
게재일2021년 01월 (BRIC 등록일 2021-01-13)
연구진국내 연구진
분야 생명과학 > 응용생물화학

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