Department of Life Science and Biochemical Engineering, SunMoon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam, 31460, Republic of Korea.
Genomics Division, National Institute of Agricultural Sciences, RDA, Jeonju, 54874, Republic of Korea.
Chembiochem. 2018 May 18;19(10):1066-1077. doi: 10.1002/cbic.201800018. Epub 2018 Apr 25.
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.
从链霉菌属中鉴定出一种新型细胞色素 P450（CYP154C8），它对不同甾体类化合物具有底物灵活性。用 CYP154C8 对这些甾体类化合物进行体外处理，揭示了具有相同甾体类化合物的有趣产物形成模式。NMR 研究表明，皮质酮的主要产物在 C21 位羟基化，而孕酮、雄烯二酮、睾酮和 11-酮孕酮仅在 16α 位羟基化。然而，孕酮的 16α-羟基化产物进一步羟基化生成二羟基化产物。16-羟基孕酮在两个位置羟基化生成二羟基化产物：2α,16α-二羟基孕酮和 6β,16α-二羟基孕酮。据我们所知，这是通过 CYP450 酶促羟化生成此类产物的首次报道。鉴于修饰甾体类化合物作为药物成分的重要性，CYP154C8 具有巨大的潜力，可用于生物生产羟化衍生物化合物，直接用于药物应用。
