Screening and characterization of a diverse panel of metagenomic imine reductases for biocatalytic reductive amination
| Autor: | James R. Marshall, Darren J. Cook, Peiyuan Yao, Nicholas J. Turner, Kirsty M. Graham, Richard A. M. Duncan, Juan Mangas-Sanchez, Simon J. Charnock, Sarah L. Montgomery, Rachel S. Heath, Ryan B. Palmer, Thomas W. Thorpe, James Finnigan |
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| Rok vydání: | 2019 |
| Předmět: |
Oxidoreductases/isolation & purification
General Chemical Engineering Ketones/chemistry Imine Stereoisomerism 010402 general chemistry 01 natural sciences Reductive amination Article Kinetic resolution chemistry.chemical_compound High-Throughput Screening Assays/methods Amines Amines/chemistry Amination Ester derivatives 010405 organic chemistry Chemistry Enantioselective synthesis Amination/drug effects General Chemistry Ketones Combinatorial chemistry Imines/metabolism 0104 chemical sciences High-Throughput Screening Assays Biocatalysis Metagenomics Imines Oxidoreductases |
| Zdroj: | Nat Chem Nature Chemistry Marshall, J R, Yao, P, Montgomery, S L, Finnigan, J D, Thorpe, T W, Palmer, R B, Mangas-sanchez, J, Duncan, R A M, Heath, R S, Graham, K M, Cook, D J, Charnock, S J & Turner, N J 2020, ' Screening and characterization of a diverse panel of metagenomic imine reductases for biocatalytic reductive amination ', Nature Chemistry, vol. 13, no. 2, 0, pp. 140-148 . https://doi.org/10.1038/s41557-020-00606-w |
| ISSN: | 1755-4349 |
| DOI: | 10.1038/s41557-020-00606-w |
| Popis: | Finding faster and simpler ways to screen protein sequence space to enable the identification of new biocatalysts for asymmetric synthesis remains both a challenge and a rate-limiting step in enzyme discovery. Biocatalytic strategies for the synthesis of chiral amines are increasingly attractive and include enzymatic asymmetric reductive amination, which offers an efficient route to many of these high-value compounds. Here we report the discovery of over 300 new imine reductases and the production of a large (384 enzymes) and sequence-diverse panel of imine reductases available for screening. We also report the development of a facile high-throughput screen to interrogate their activity. Through this approach we identified imine reductase biocatalysts capable of accepting structurally demanding ketones and amines, which include the preparative synthesis of N-substituted β-amino ester derivatives via a dynamic kinetic resolution process, with excellent yields and stereochemical purities. [Figure not available: see fulltext.] |
| Databáze: | OpenAIRE |
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