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Tracking Down a New Steroid‐Hydroxylating Promiscuous Cytochrome P450: CYP154C8 from Streptomyces sp. W2233‐SM
Author(s) -
Dangi Bikash,
Kim KiHwa,
Kang SangHo,
Oh TaeJin
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800018
Subject(s) - hydroxylation , cytochrome p450 , steroid , chemistry , androstenedione , yield (engineering) , stereochemistry , streptomyces , testosterone (patch) , natural product , biochemistry , biology , metabolism , enzyme , hormone , endocrinology , androgen , materials science , bacteria , metallurgy , genetics
CYP154C8 from Streptomyces sp. has been identified as a new cytochrome P450 with substrate flexibility towards different sets of steroids. In vitro treatment of these steroids with CYP154C8 revealed interesting product formation patterns with the same group of steroids. NMR study revealed the major product of corticosterone to be hydroxylated at the C21 position, whereas progesterone, androstenedione, testosterone, and 11‐ketoprogesterone were exclusively hydroxylated at the 16α position. However, the 16α‐hydroxylated product of progesterone was further hydroxylated to yield dihydroxylated products. 16‐hydroxyprogesterone was hydroxylated at two positions to yield dihydroxylated products: 2α,16α‐dihydroxyprogesterone and 6β,16α‐dihydroxyprogesterone. To the best of our knowledge, this is the first report of generation of such products through enzymatic hydroxylation by a CYP450. In view of the importance of modified steroids as pharmaceutical components, CYP154C8 has immense potential for utilization in bioproduction of hydroxylated derivative compounds to be directly employed for pharmaceutical applications.