Cytochrome P450 enzyme RosC catalyzes a multistep oxidation reaction to form the non-active compound 20-carboxyrosamicin
Cytochrome P450 enzyme RosC catalyzes a multistep oxidation reaction to form the non-active compound 20-carboxyrosamicin
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DOI：
10.1093/femsle/fnx110
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发表时间：
2017-06-01
影响因子：
2.1
通讯作者：
Anzai, Yojiro
中科院分区：
文献类型：
--
作者：
Iizaka, Yohei;Takeda, Rina;Anzai, Yojiro
细胞色素P450酶RosC催化由玫瑰小单孢菌IFO 13697产生的16元大环内酯抗生素玫瑰霉素的生物合成中的两步羟基化和醇氧化氧化反应，以形成C-20甲酰基。RosC被认为参与了20-carboxyrosamicin的形成，因为它已经从M.玫瑰花。在此，我们证实了RosC具有催化活性，E.表达RosC的大肠杆菌将玫瑰霉素转化为20-羧基玫瑰霉素。因此，研究表明，RosC是一种多功能P450，可以催化三步氧化反应，导致玫瑰霉素生物合成途径中大环内酯环C-20处形成羟基、甲酰基和羧基。此外，细胞色素P450酶TylI也将玫瑰霉素转化为20-羧基玫瑰霉素，TylI参与由草莓链霉菌ATCC 19609产生的16元大环内酯类抗生素泰乐菌素的甲酰基的形成。
The cytochrome P450 enzyme RosC catalyzes a two-step, hydroxylation and alcohol oxidation, oxidation reaction to form the C-20 formyl group in the biosynthesis of a 16-membered macrolide antibiotic rosamicin produced by Micromonospora rosaria IFO13697. RosC is presumed to be involved in the formation of 20-carboxyrosamicin because it has been isolated from the culture broth of M. rosaria. Here, we confirmed that RosC has catalytic activity, with E. coli expressing RosC converting rosamicin into 20-carboxyrosamicin. Therefore, it was revealed that RosC is a multifunctional P450 that catalyzes a three-step oxidation reaction that leads to the formation of the hydroxyl group, formyl group and carboxyl group at C-20 on the macrolactone ring in the rosamicin biosynthetic pathway. Moreover, the cytochrome P450 enzyme TylI, which is involved in formation of the formyl group of a 16-membered macrolide antibiotic tylosin produced by Streptomyces fradiae ATCC 19609, also converted rosamicin into 20-carboxyrosamicin.