Enantioselective α-Hydroxylation of 2-Arylacetic Acid Derivatives and Buspirone Catalyzed by Engineered Cytochrome P450 BM-3

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Enantioselective alpha-hydroxylation of 2-arylacetic acid derivatives and buspirone catalyzed by engineered cytochrome P450 BM-3.

Here we report that an engineered microbial cytochrome P450 BM-3 (CYP102A subfamily) efficiently catalyzes the alpha-hydroxylation of phenylacetic acid esters. This P450 BM-3 variant also produces the authentic human metabolite of buspirone, R-6-hydroxybuspirone, with 99.5% ee.

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Cytochrome P450 BM-3 from Bacillus megaterium catalyzed NADPH-supported indole hydroxylation under alkaline conditions with homotropic cooperativity toward indole. The activity was also found with the support of H2O2, tert-butyl hydroperoxide (tBuOOH), or cumene hydroperoxide (CuOOH). Enhanced activity and heterotropic cooperativity were observed in CuOOH-supported hydroxylation, and both the H...

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Enantioselective intramolecular C-H amination catalyzed by engineered cytochrome P450 enzymes in vitro and in vivo.

Iron containing monooxygenases play diverse roles in nature, ranging from the primary metabolic functions of alkane hydroxylases to the xenobiotic detoxification and secondary metabolic roles of cytochrome P450 enzymes..[1] Common to these enzymes is the ability to reductively activate molecular oxygen to generate highly electrophilic oxygen species, whose reactivity is comparable with that of ...

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Supporting Information Stereoselective hydroxylation of an achiral cyclopentanecarboxylic acid derivative using engineered P450s BM-3

a Institut für Organische Chemie der Technischen Universität Graz, Stremayrgasse 16, A-8010 Graz, Austria. Fax: +43 316 873 8740; Tel: +43 316 873 8751; E-mail: [email protected] b Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Fax: +1 626 568 8743; Tel: +1 626 395 4162; E-mail: [email protected] c Institut für Molek...

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ژورنال

عنوان ژورنال: Journal of the American Chemical Society

سال: 2006

ISSN: 0002-7863,1520-5126

DOI: 10.1021/ja061261x