期刊
CHEMBIOCHEM
卷 15, 期 17, 页码 2556-2562出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201402286
关键词
cyclopropanation; cytochromes; enzyme catalysis; metalloenzyme
资金
- Gordon and Betty Moore Foundation [GBMF2809]
- FWF Schroedinger fellowship [J3327-B21]
- National Institutes of Health [5F32M106618, F32M101792]
- Department of Defense through National Defense Science & Engineering Graduate Fellowship Program
- National Science Foundation through Graduate Research Fellowship Program
- Austrian Science Fund (FWF) [J 3327] Funding Source: researchfish
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [F32GM101792, F32GM106618] Funding Source: NIH RePORTER
Recent work has shown that engineered variants of cytochrome P450(BM3) (CYP102A1) efficiently catalyze non-natural reactions, including carbene and nitrene transfer reactions. Given the broad substrate range of natural P450 enzymes, we set out to explore if this diversity could be leveraged to generate a broad panel of new catalysts for olefin cyclopropanation (i.e., carbene transfer). Here, we took a step towards this goal by characterizing the carbene transfer activities of four new wildtype P450s that have different native substrates. All four were active and exhibited a range of product selectivities in the model reaction: cyclopropanation of styrene by using ethyl diazoacetate (EDA). Previous work on P450(BM3) demonstrated that mutation of the axial coordinating cysteine, universally conserved among P450 enzymes, to a serine residue, increased activity for this non-natural reaction. The equivalent mutation in the selected P450s was found to activate carbene transfer chemistry both in vitro and in vivo. Furthermore, serum albumins complexed with hemin were also found to be efficient in vitro cyclopropanation catalysts.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据