Journal
CATALYSIS SCIENCE & TECHNOLOGY
Volume 8, Issue 18, Pages 4638-4644Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c8cy01448e
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Funding
- National Natural Science Foundation of China [21672063, 21536004]
- Fundamental Research Fund for the Central Universities [222201514039]
- Science and Technology Commission of Shanghai Municipality [15JC1400403]
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The P450-mediated asymmetric hydroxylation of inert C-H bonds is a chemically challenging reaction. Self-sufficient P450(LaMO) 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 P450(LaMO), 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 P450(LaMO)-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.
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