Insights into the complex biosynthesis of the leupyrrins in Sorangium cellulosum So ce690.

2.50
HDL Handle:
http://hdl.handle.net/10033/146376
Title:
Insights into the complex biosynthesis of the leupyrrins in Sorangium cellulosum So ce690.
Authors:
Kopp, Maren; Irschik, Herbert; Gemperlein, Katja; Buntin, Kathrin; Meiser, Peter; Weissman, Kira J; Bode, Helge B; Müller, Rolf
Abstract:
The anti-fungal leupyrrins are secondary metabolites produced by several strains of the myxobacterium Sorangium cellulosum. These intriguing compounds incorporate an atypically substituted γ-butyrolactone ring, as well as pyrrole and oxazolinone functionalities, which are located within an unusual asymmetrical macrodiolide. Previous feeding studies revealed that this novel structure arises from the homologation of four distinct structural units, nonribosomally-derived peptide, polyketide, isoprenoid and a dicarboxylic acid, coupled with modification of the various building blocks. Here we have attempted to reconcile the biosynthetic pathway proposed on the basis of the feeding studies with the underlying enzymatic machinery in the S. cellulosum strain So ce690. Gene products can be assigned to many of the suggested steps, but inspection of the gene set provokes the reconsideration of several key transformations. We support our analysis by the reconstitution in vitro of the biosynthesis of the pyrrole carboxylic starter unit along with gene inactivation. In addition, this study reveals that a significant proportion of the genes for leupyrrin biosynthesis are located outside the core cluster, a 'split' organization which is increasingly characteristic of the myxobacteria. Finally, we report the generation of four novel deshydroxy leupyrrin analogues by genetic engineering of the pathway.
Affiliation:
Helmholtz Institute for Pharmaceutical Research, Helmholtz Center for Infection Research and Department of Pharmaceutical Biotechnology, Saarland University, PO Box 151150, 66041 Saarbrücken, Germany.
Citation:
Insights into the complex biosynthesis of the leupyrrins in Sorangium cellulosum So ce690. 2011, 7 (5):1549-63 Mol Biosyst
Journal:
Molecular bioSystems
Issue Date:
May-2011
URI:
http://hdl.handle.net/10033/146376
DOI:
10.1039/c0mb00240b
PubMed ID:
21365089
Type:
Article
Language:
en
ISSN:
1742-2051
Appears in Collections:
Publications of the division Mikrobielle Naturstoffe (MINS)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorKopp, Marenen
dc.contributor.authorIrschik, Herberten
dc.contributor.authorGemperlein, Katjaen
dc.contributor.authorBuntin, Kathrinen
dc.contributor.authorMeiser, Peteren
dc.contributor.authorWeissman, Kira Jen
dc.contributor.authorBode, Helge Ben
dc.contributor.authorMüller, Rolfen
dc.date.accessioned2011-10-21T12:35:38Z-
dc.date.available2011-10-21T12:35:38Z-
dc.date.issued2011-05-
dc.identifier.citationInsights into the complex biosynthesis of the leupyrrins in Sorangium cellulosum So ce690. 2011, 7 (5):1549-63 Mol Biosysten
dc.identifier.issn1742-2051-
dc.identifier.pmid21365089-
dc.identifier.doi10.1039/c0mb00240b-
dc.identifier.urihttp://hdl.handle.net/10033/146376-
dc.description.abstractThe anti-fungal leupyrrins are secondary metabolites produced by several strains of the myxobacterium Sorangium cellulosum. These intriguing compounds incorporate an atypically substituted γ-butyrolactone ring, as well as pyrrole and oxazolinone functionalities, which are located within an unusual asymmetrical macrodiolide. Previous feeding studies revealed that this novel structure arises from the homologation of four distinct structural units, nonribosomally-derived peptide, polyketide, isoprenoid and a dicarboxylic acid, coupled with modification of the various building blocks. Here we have attempted to reconcile the biosynthetic pathway proposed on the basis of the feeding studies with the underlying enzymatic machinery in the S. cellulosum strain So ce690. Gene products can be assigned to many of the suggested steps, but inspection of the gene set provokes the reconsideration of several key transformations. We support our analysis by the reconstitution in vitro of the biosynthesis of the pyrrole carboxylic starter unit along with gene inactivation. In addition, this study reveals that a significant proportion of the genes for leupyrrin biosynthesis are located outside the core cluster, a 'split' organization which is increasingly characteristic of the myxobacteria. Finally, we report the generation of four novel deshydroxy leupyrrin analogues by genetic engineering of the pathway.en
dc.language.isoenen
dc.subject.mesh4-Butyrolactoneen
dc.subject.meshAmino Acid Sequenceen
dc.subject.meshBiosynthetic Pathwaysen
dc.subject.meshDNA, Bacterialen
dc.subject.meshElectrophoresis, Polyacrylamide Gelen
dc.subject.meshMolecular Sequence Dataen
dc.subject.meshMolecular Structureen
dc.subject.meshMultigene Familyen
dc.subject.meshMyxococcalesen
dc.subject.meshPlant Proteinsen
dc.subject.meshPolymerase Chain Reactionen
dc.subject.meshSequence Homology, Amino Aciden
dc.subject.meshSpectrometry, Mass, Matrix-Assisted Laser Desorption-Ionizationen
dc.titleInsights into the complex biosynthesis of the leupyrrins in Sorangium cellulosum So ce690.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Institute for Pharmaceutical Research, Helmholtz Center for Infection Research and Department of Pharmaceutical Biotechnology, Saarland University, PO Box 151150, 66041 Saarbrücken, Germany.en
dc.identifier.journalMolecular bioSystemsen

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