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

Eunji Kim, Myoung Chong Song, Myoun Su Kim, Ji Yoon Beom, Eun Yeol Lee, Dong Myung Kim, Sang Jip Nam, Yeo Joon Yoon

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9 Scopus citations


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.

Original languageEnglish
Pages (from-to)2014-2021
Number of pages8
JournalJournal of Natural Products
Issue number8
StatePublished - 26 Aug 2016

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© 2016 The American Chemical Society and American Society of Pharmacognosy.


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