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基于 P450 的生物催化剂应用的最新进展。

Recent developments in the application of P450 based biocatalysts.

机构信息

Metabolic Engineering Research Laboratory, Science and Engineering Institutes, Agency for Science, Technology, and Research, Singapore.

Metabolic Engineering Research Laboratory, Science and Engineering Institutes, Agency for Science, Technology, and Research, Singapore; Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 South Mathews Ave, Urbana, IL 61801, United States; Departments of Chemistry, Biochemistry, and Bioengineering, and Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 600 South Mathews Ave, Urbana, IL 61801, United States.

出版信息

Curr Opin Chem Biol. 2018 Apr;43:1-7. doi: 10.1016/j.cbpa.2017.08.006. Epub 2017 Oct 27.

DOI:10.1016/j.cbpa.2017.08.006
PMID:29100098
Abstract

Cytochrome P450 monooxygenases (P450s) catalyze regioselective and stereoselective oxidative modifications of a wide variety of substrates, and are involved in the biosynthesis of many natural products. Despite the complex requirements of the P450 reaction system and its intransigence to recombinant expression, the promise of harnessing P450 reactivity for the industrial-scale production of specialty chemicals has led to much effort invested in P450 engineering. Here we review recent developments (between 2015 and 2017) in the application of P450s and their engineered variants as biocatalysts. We describe strategies for the reconstitution of P450 activity in heterologous microbial hosts, and the expanding repertoire of non-natural reactions catalyzed by engineered P450s.

摘要

细胞色素 P450 单加氧酶(P450s)催化各种底物的区域选择性和立体选择性氧化修饰,并且参与许多天然产物的生物合成。尽管 P450 反应体系的要求复杂,并且其对重组表达的顽固不化,但利用 P450 反应性大规模生产特种化学品的前景,促使人们投入大量精力进行 P450 工程。在这里,我们回顾了 2015 年至 2017 年期间 P450 及其工程变体作为生物催化剂的应用的最新进展。我们描述了在异源微生物宿主中重建 P450 活性的策略,以及工程 P450 催化的非天然反应的扩展 repertoire。

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