{"title":"Expanding the repertoire of imine reductases by mining divergent biosynthetic pathways for promiscuous reactivity","authors":"Godwin A. Aleku, Florian Hollfelder","doi":"10.1016/j.checat.2024.101160","DOIUrl":null,"url":null,"abstract":"Imine reductases (IREDs) are invaluable catalysts for enantioselective imine reduction and reductive amination of carbonyl compounds. Their synthetic versatility is, however, limited by their substrate scope, and new IREDs are needed. Current IREDs are closely related to the initially characterized enzymes, as their discovery has been driven by sequence homology searches. Here, we demonstrate a <em>functional</em> genomics approach based on biosynthetic promiscuity, guided by the identification of C=N reducing enzymes acting on large, complex substrates in biosynthetic pathways. These substrate-promiscuous biocatalysts share low homology to existing IREDs and fall into distinct functional enzyme families, yet they catalyze the hydrogenation of non-native imines as well as the reductive amination of simple ketones. Venturing further into sequence space without the constraints of close homology, but instead guided by functional promiscuity, has thus led us to distinct, previously unrecognized and unexplored areas of sequence space for mining IREDs for synthesis.","PeriodicalId":53121,"journal":{"name":"Chem Catalysis","volume":"235 1","pages":""},"PeriodicalIF":11.5000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chem Catalysis","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.checat.2024.101160","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Imine reductases (IREDs) are invaluable catalysts for enantioselective imine reduction and reductive amination of carbonyl compounds. Their synthetic versatility is, however, limited by their substrate scope, and new IREDs are needed. Current IREDs are closely related to the initially characterized enzymes, as their discovery has been driven by sequence homology searches. Here, we demonstrate a functional genomics approach based on biosynthetic promiscuity, guided by the identification of C=N reducing enzymes acting on large, complex substrates in biosynthetic pathways. These substrate-promiscuous biocatalysts share low homology to existing IREDs and fall into distinct functional enzyme families, yet they catalyze the hydrogenation of non-native imines as well as the reductive amination of simple ketones. Venturing further into sequence space without the constraints of close homology, but instead guided by functional promiscuity, has thus led us to distinct, previously unrecognized and unexplored areas of sequence space for mining IREDs for synthesis.
期刊介绍:
Chem Catalysis is a monthly journal that publishes innovative research on fundamental and applied catalysis, providing a platform for researchers across chemistry, chemical engineering, and related fields. It serves as a premier resource for scientists and engineers in academia and industry, covering heterogeneous, homogeneous, and biocatalysis. Emphasizing transformative methods and technologies, the journal aims to advance understanding, introduce novel catalysts, and connect fundamental insights to real-world applications for societal benefit.