Abstract
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 language | English |
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Pages (from-to) | 2014-2021 |
Number of pages | 8 |
Journal | Journal of Natural Products |
Volume | 79 |
Issue number | 8 |
DOIs | |
State | Published - 26 Aug 2016 |
Bibliographical note
Publisher Copyright:© 2016 The American Chemical Society and American Society of Pharmacognosy.