2.50
Hdl Handle:
http://hdl.handle.net/10033/12426
Title:
A unique mechanism for methyl ester formation via an amide intermediate found in myxobacteria.
Authors:
Müller, Inga; Weinig, Stefan; Steinmetz, Heinrich; Kunze, Birgitte; Veluthoor, Sheeba; Mahmud, Taifo; Müller, Rolf
Abstract:
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):1197-205
Issue Date:
1-Aug-2006
URI:
http://hdl.handle.net/10033/12426
DOI:
10.1002/cbic.200600057
PubMed ID:
16807964
Type:
Article
Language:
en
ISSN:
1439-4227
Appears in Collections:
collections of the research group microbial communication (KOM)

Full metadata record

DC FieldValue Language
dc.contributor.authorMüller, Inga-
dc.contributor.authorWeinig, Stefan-
dc.contributor.authorSteinmetz, Heinrich-
dc.contributor.authorKunze, Birgitte-
dc.contributor.authorVeluthoor, Sheeba-
dc.contributor.authorMahmud, Taifo-
dc.contributor.authorMüller, Rolf-
dc.date.accessioned2007-06-25T13:00:31Z-
dc.date.available2007-06-25T13:00:31Z-
dc.date.issued2006-08-01-
dc.identifier.citationChembiochem 2006, 7(8):1197-205en
dc.identifier.issn1439-4227-
dc.identifier.pmid16807964-
dc.identifier.doi10.1002/cbic.200600057-
dc.identifier.urihttp://hdl.handle.net/10033/12426-
dc.description.abstractSecondary 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.en
dc.format.extent177165 bytes-
dc.format.mimetypeapplication/pdf-
dc.language.isoenen
dc.titleA unique mechanism for methyl ester formation via an amide intermediate found in myxobacteria.en
dc.typeArticleen
dc.format.digYES-
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