Characterization of the Two Methylation Steps Involved in the Biosynthesis of Mycinose in Tylosin
| Autor: | Eunji Kim, Sang Jip Nam, Ji Yoon Beom, Myoung Chong Song, Myoun Su Kim, Dong-Myung Kim, Eun Yeol Lee, Yeo Joon Yoon |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
S-Adenosylmethionine Stereochemistry Macrocin 030106 microbiology Mutant Pharmaceutical Science Tylosin medicine.disease_cause Leucomycins Methylation Analytical Chemistry 03 medical and health sciences chemistry.chemical_compound Biosynthesis Drug Discovery medicine Moiety Hexoses Pharmacology Mutation Molecular Structure biology Organic Chemistry Methyltransferases Streptomyces fradiae biology.organism_classification Streptomyces Anti-Bacterial Agents 030104 developmental biology Complementary and alternative medicine chemistry Biochemistry Molecular Medicine |
| Zdroj: | Journal of Natural Products. 79:2014-2021 |
| ISSN: | 1520-6025 0163-3864 |
| DOI: | 10.1021/acs.jnatprod.6b00267 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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