2β- and 16β-hydroxylase activity of CYP11A1 and direct stimulatory effect of estrogens on pregnenolone formation
作者： A. Mosa , J. Neunzig , A. Gerber , J. Zapp , F. Hannemann
DOI: 10.1016/J.JSBMB.2015.02.014
关键词:
摘要: The biosynthesis of steroid hormones in vertebrates is initiated by the cytochrome P450 CYP11A1, which performs side-chain cleavage cholesterol thereby producing pregnenolone. In this study, we report a direct stimulatory effect estrogens estradiol and estrone onto pregnenolone formation reconstituted vitro system consisting purified CYP11A1 its natural redox partners. We demonstrated new products from 11-deoxycorticosterone (DOC), androstenedione, testosterone dehydroepiandrosterone (DHEA) during reaction catalyzed CYP11A1. addition, also established an Escherichia coli-based whole-cell biocatalytic partners to obtain sufficient yields for NMR-characterization. Our results indicate that addition previously described 6β-hydroxylase activity, possesses 2β-hydroxylase activity towards DOC androstenedione as well 16β-hydroxylase DHEA. showed able perform 6β-hydroxylation testosterone, has been predominantly attributed CYP3A4. are first evidence sex positively regulate overall production suggesting need reassess role hormone substrate-dependent mechanistic properties.
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