Biosynthesis of crocacin involves an unusual hydrolytic release domain showing similarity to condensation domains.

2.50
Hdl Handle:
http://hdl.handle.net/10033/575933
Title:
Biosynthesis of crocacin involves an unusual hydrolytic release domain showing similarity to condensation domains.
Authors:
Müller, Stefan; Rachid, Shwan; Hoffmann, Thomas; Surup, Frank; Volz, Carsten; Zaburannyi, Nestor; Müller, Rolf
Abstract:
The crocacins are potent antifungal and cytotoxic natural compounds from myxobacteria of the genus Chondromyces. Although total synthesis approaches have been reported, the molecular and biochemical basis guiding the formation of the linear crocacin scaffold has remained unknown. Along with the identification and functional analysis of the crocacin biosynthetic gene cluster from Chondromyces crocatus Cm c5, we here present the identification and biochemical characterization of an unusual chain termination domain homologous to condensation domains responsible for hydrolytic release of the product from the assembly line. In particular, gene inactivation studies and in vitro experiments using the heterologously produced domain CroK-C2 confirm this surprising role giving rise to the linear carboxylic acid. Additionally, we determined the kinetic parameters of CroK-C2 by monitoring hydrolytic cleavage of the substrate mimic N-acetylcysteaminyl-crocacin B using an innovative high-performance liquid chromatography mass spectrometry-based assay.
Affiliation:
Helmholtz Institute for Pharmaceutical Research Saarland,Saarbru¨ cken, Saarland 66123, Germany.
Citation:
Biosynthesis of crocacin involves an unusual hydrolytic release domain showing similarity to condensation domains. 2014, 21 (7):855-65 Chem. Biol.
Journal:
Chemistry & biology
Issue Date:
17-Jul-2014
URI:
http://hdl.handle.net/10033/575933
DOI:
10.1016/j.chembiol.2014.05.012
PubMed ID:
24981773
Type:
Article
Language:
en
ISSN:
1879-1301
Appears in Collections:
publications of the department drug design and optimization (HIPS]DDOP)

Full metadata record

DC FieldValue Language
dc.contributor.authorMüller, Stefanen
dc.contributor.authorRachid, Shwanen
dc.contributor.authorHoffmann, Thomasen
dc.contributor.authorSurup, Franken
dc.contributor.authorVolz, Carstenen
dc.contributor.authorZaburannyi, Nestoren
dc.contributor.authorMüller, Rolfen
dc.date.accessioned2015-08-25T13:54:50Zen
dc.date.available2015-08-25T13:54:50Zen
dc.date.issued2014-07-17en
dc.identifier.citationBiosynthesis of crocacin involves an unusual hydrolytic release domain showing similarity to condensation domains. 2014, 21 (7):855-65 Chem. Biol.en
dc.identifier.issn1879-1301en
dc.identifier.pmid24981773en
dc.identifier.doi10.1016/j.chembiol.2014.05.012en
dc.identifier.urihttp://hdl.handle.net/10033/575933en
dc.description.abstractThe crocacins are potent antifungal and cytotoxic natural compounds from myxobacteria of the genus Chondromyces. Although total synthesis approaches have been reported, the molecular and biochemical basis guiding the formation of the linear crocacin scaffold has remained unknown. Along with the identification and functional analysis of the crocacin biosynthetic gene cluster from Chondromyces crocatus Cm c5, we here present the identification and biochemical characterization of an unusual chain termination domain homologous to condensation domains responsible for hydrolytic release of the product from the assembly line. In particular, gene inactivation studies and in vitro experiments using the heterologously produced domain CroK-C2 confirm this surprising role giving rise to the linear carboxylic acid. Additionally, we determined the kinetic parameters of CroK-C2 by monitoring hydrolytic cleavage of the substrate mimic N-acetylcysteaminyl-crocacin B using an innovative high-performance liquid chromatography mass spectrometry-based assay.en
dc.language.isoenen
dc.subject.meshBiological Productsen
dc.subject.meshGenetic Engineeringen
dc.subject.meshHydrolysisen
dc.subject.meshModels, Biologicalen
dc.subject.meshMolecular Sequence Dataen
dc.subject.meshMultigene Familyen
dc.subject.meshMyxococcalesen
dc.subject.meshPeptide Synthasesen
dc.subject.meshPolyenesen
dc.subject.meshProtein Structure, Tertiaryen
dc.titleBiosynthesis of crocacin involves an unusual hydrolytic release domain showing similarity to condensation domains.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Institute for Pharmaceutical Research Saarland,Saarbru¨ cken, Saarland 66123, Germany.en
dc.identifier.journalChemistry & biologyen
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