A unique mechanism for methyl ester formation via an amide intermediate found in myxobacteria.
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Authors
Müller, IngaWeinig, Stefan
Steinmetz, Heinrich
Kunze, Birgitte
Veluthoor, Sheeba
Mahmud, Taifo
Müller, Rolf
Issue Date
2006-08-01
Metadata
Show full item recordAbstract
Secondary metabolism involves a broad diversity of biochemical reactions that result in a wide variety of biologically active compounds. Terminal amide formation during the biosynthesis of the myxobacterial electron-transport inhibitor, myxothiazol, was analyzed by heterologous expression of the unique nonribosomal-peptide synthetase, MtaG, and incubation with a synthesized substrate mimic. These experiments provide evidence that the terminal amide is formed from a carrier protein-bound myxothiazol acid that is thioesterified to MtaF. This intermediate is transformed to an amide by extension with glycine and subsequent oxidative cleavage by MtaG. The final steps of melithiazol assembly involve a highly similar protein-bound intermediate (attached to MelF, a homologue of MtaF), which is transformed to an amide by MelG (homologue of MtaG). In this study, we also show that the amide moiety of myxothiazol A can be hydrolyzed in vivo to the formerly unknown free myxothiazol acid by heterologous expression of melJ in the myxothiazol producer Stigmatella aurantiaca DW4/3-1. The methyltransferase MelK can finally methylate the acid to give rise to the methyl ester, which is produced as the final product in the melithiazol A biosynthetic pathway. These experiments clarify the role of MelJ and MelK during melithiazol assembly.Citation
Chembiochem 2006, 7(8):1197-205PubMed ID
16807964Type
ArticleLanguage
enISSN
1439-4227ae974a485f413a2113503eed53cd6c53
10.1002/cbic.200600057
Scopus Count
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