Characterization of the Two Methylation Steps Involved in the Biosynthesis of Mycinose in Tylosin

详细信息    查看全文

• 作者：Eunji Kim ; Myoung Chong Song ; Myoun Su Kim ; Ji Yoon Beom ; Eun Yeol Lee ; Dong-Myung Kim ; Sang-Jip Nam ; Yeo Joon Yoon
• 刊名：Journal of Natural Products
• 出版年：2016
• 出版时间：August 26, 2016
• 年：2016
• 卷：79
• 期：8
• 页码：2014-2021
• 全文大小：389K
• 年卷期：0
• ISSN：1520-6025

文摘

The S-adenosyl-l-methionine-dependent O-methyltransferases TylE and TylF catalyze the last two methylation reactions in the tylosin biosynthetic pathway of Streptomyces fradiae. It has long been known that the TylE-catalyzed C2‴-O-methylation of the 6-deoxy-d-allose bound to demethylmacrocin or demethyllactenocin precedes the TylF-catalyzed C3‴-O-methylation of the d-javose (C2‴-O-methylated 6-deoxy-d-allose) attached to macrocin or lactenocin. This study reveals the unexpected substrate promiscuity of TylE and TylF responsible for the biosynthesis of d-mycinose (C3‴-O-methylated d-javose) in tylosin through the identification of a new minor intermediate 2‴-O-demethyldesmycosin (2; 3‴-methyl-demethyllactenocin), which lacks a 2‴-O-methyl group on the mycinose moiety of desmycosin, along with 2‴-O-demethyltylosin (1; 3‴-methyl-demethylmacrocin) that was previously detected from the S. fradiae mutant containing a mutation in the tylE gene. These results unveil the unique substrate flexibility of TylE and TylF and demonstrate their potential for the engineered biosynthesis of novel glycosylated macrolide derivatives.