C-26 vs. C-27 hydroxylation of insect steroid hormones: regioselectivity of a microsomal cytochrome P450 from a hormone-resistant cell line.
作者： Hartmut Kayser , Philipp Eilinger , Philippe Piechon , Trixie Wagner
DOI: 10.1016/J.ABB.2011.06.011
关键词:
摘要: Hydroxylation of steroids at one the side chain terminal methyl groups, commonly linked to C-26, represents an important regulatory step established in many phyla. Discrimination between two sites, C-26 and C-27, requires knowing stereochemistry products. 26-Hydroxylation insect steroid hormone 20-hydroxyecdysone by a microsomal cytochrome P450 was previously found be responsible for hormonal resistance Chironomus cell line mainly producing (25S)-epimer 20,26-dihydroxyecdysone. Here, we studied 25-desoxy analog 20-hydroxyecdysone, ponasterone A, elucidate expected 26-hydroxy product, inokosterone, which occurs as C-25 epimers nature. We identified predominant metabolite R epimer inokosterone on comparison RP-HPLC with (25R)- (25S)-epimers confirmed X-ray crystallography. (25R)-inokosterone further oxidized 26-aldehyde mass spectroscopy, borohydride reduction metabolic transformation 26-carboxylic acid. The its aldehyde were minor With substrate, newly (25R)-epimer 20,26-dihydroxyecdysone product. In conclusion, present stereochemical studies revealed high regioselectivity enzyme hydroxylate both same group, denoted C-27.
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