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Issue 18, 2018
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Engineering P450LaMO stereospecificity and product selectivity for selective C–H oxidation of tetralin-like alkylbenzenes

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Abstract

The P450-mediated asymmetric hydroxylation of inert C–H bonds is a chemically challenging reaction. Self-sufficient P450LaMO from the CYP116B subfamily could catalyze the transformation of 1,2,3,4-tetrahydronaphthalene to (S)-tetralol, despite its poor enantioselectivity (er 66 : 34) and product selectivity (the ratio of alcohol and ketone, ak, 76 : 24). To improve the selectivity, phenylalanine scanning and further protein engineering were performed to reshape the active pocket of P450LaMO, resulting in a mutant (T121V/Y385F/M391L) with not only improved (S)-enantioselectivity (er 98 : 2) but also excellent product selectivity (ak 99 : 1), in contrast to another mutant L97F/T121F/E282V/T283Y with complementary (R)-enantioselectivity (er 23 : 77). Moreover, the enantiopure (S)-alcohols formed by the P450LaMO-catalyzed oxidation of a series of alkylbenzenes are potentially important building blocks in the pharmaceutical industry. This Phe-based enantioselectivity engineering used for reshaping the active pocket of P450s could provide a guide to the protein evolution of other CYP116B members.

Graphical abstract: Engineering P450LaMO stereospecificity and product selectivity for selective C–H oxidation of tetralin-like alkylbenzenes

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Publication details

The article was received on 12 Jul 2018, accepted on 03 Aug 2018 and first published on 03 Aug 2018


Article type: Paper
DOI: 10.1039/C8CY01448E
Citation: Catal. Sci. Technol., 2018,8, 4638-4644
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    Engineering P450LaMO stereospecificity and product selectivity for selective C–H oxidation of tetralin-like alkylbenzenes

    R. Li, A. Li, J. Zhao, Q. Chen, N. Li, H. Yu and J. Xu, Catal. Sci. Technol., 2018, 8, 4638
    DOI: 10.1039/C8CY01448E

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