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Fuchs S.W.,Merck Stiftungsprofessur fur Molekulare Biotechnologie | Grundmann F.,Merck Stiftungsprofessur fur Molekulare Biotechnologie | Kurz M.,Sanofi S.A. | Kaiser M.,Swiss Tropical and Public Health Institute | Bode H.B.,Merck Stiftungsprofessur fur Molekulare Biotechnologie
ChemBioChem | Year: 2014

The structure of the fabclavines - unique mixtures of nonribosomally derived peptide-polyketide hybrids connected to an unusual polyamino moiety - has been solved by detailed NMR and MS methods. These compounds have been identified in two different entomopathogenic Xenorhabdus strains, thereby leading also to the identification of the fabclavine biosynthesis gene cluster. Detailed analysis of these clusters and initial mutagenesis experiments allowed the prediction of a biosynthesis pathway in which the polyamino moiety is derived from an unusual type of fatty acid synthase that is normally involved in formation of polyunsaturated fatty acids. As fabclavines show broad-spectrum activity against bacteria, fungi, and other eukaryotic cells, they might act as "protection factors" against all kinds of food competitors during the complex life cycle of Xenorhabdus, its nematode host, and their insect prey. A novel tri(hy)brid: The structures and biosynthesis of fabclavines, novel peptide-polyketide-polyamino natural products from entomopathogenic Xenorhabdus, were elucidated. They exhibit broad-spectrum biological activity and an unusual polyamino moiety derived from polyunsaturated fatty-acid-like biosynthesis. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Fuchs S.W.,Merck Stiftungsprofessur fur Molekulare Biotechnologie | Bozhuyuk K.A.J.,Merck Stiftungsprofessur fur Molekulare Biotechnologie | Kresovic D.,Merck Stiftungsprofessur fur Molekulare Biotechnologie | Grundmann F.,Merck Stiftungsprofessur fur Molekulare Biotechnologie | And 4 more authors.
Angewandte Chemie - International Edition | Year: 2013

Overlooked, but widespread! A new class of ketosynthases (DarB) involved in the biosynthesis of 1,3-cyclohexanediones and dialkylresorcinols has been identified and characterized in detail. The presence of homologues in 89 different bacteria, including several pathogens, reveals that DarB as well as the corresponding natural products might be widespread, thus presenting a new but so far overlooked pathway to natural products. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Morinaka B.I.,ETH Zurich | Vagstad A.L.,ETH Zurich | Helf M.J.,ETH Zurich | Gugger M.,Institute Pasteur Paris | And 4 more authors.
Angewandte Chemie - International Edition | Year: 2014

PoyD is a radical S-adenosyl methionine epimerase that introduces multiple D-configured amino acids at alternating positions into the highly complex marine peptides polytheonamide A and B. This novel post-translational modification contributes to the ability of the polytheonamides to form unimolecular minimalistic ion channels and its cytotoxic activity at picomolar levels. Using a genome mining approach we have identified additional PoyD homologues in various bacteria. Three enzymes were expressed in E. coli with their cognate as well as engineered peptide precursors and shown to introduce diverse D-amino acid patterns into all-L peptides. The data reveal a family of architecturally and functionally distinct enzymes that exhibit high regioselectivity, substrate promiscuity, and irreversible action and thus provide attractive opportunities for peptide engineering. A radical change: Radical S-adenosyl methionine (SAM) epimerases is a new family of architecturally and functionally distinct bacterial enzymes. Three members from cyanobacteria were shown to introduce diverse D-amino acid patterns into all-L peptides. Their high regioselectivity, substrate promiscuity, and irreversible action provide interesting opportunities for peptide engineering. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Schoner T.A.,Merck Stiftungsprofessur fur Molekulare Biotechnologie | Fuchs S.W.,Merck Stiftungsprofessur fur Molekulare Biotechnologie | Schonau C.,Sanofi S.A. | Bode H.B.,Merck Stiftungsprofessur fur Molekulare Biotechnologie
Microbial Biotechnology | Year: 2014

Bacteria from the Bacteroidetes phylum are known producers of the chemotaxonomic relevant flexirubins. These orange pigments comprise a non-isoprenoid aryl-polyene carboxylic acid esterified with a dialkylresorcinol. Herein, we report a gene cluster from Chitinophaga pinensis encoding the biosynthesis of the polyene moiety and the biochemical characterization of a tyrosine ammonia-lyase and a 4-coumarate-CoA ligase responsible for the initiation of the polyene biosynthesis. Additionally, the flexirubin of C.pinensis was characterized by a combination of feeding experiments, high-performance liquid chromatography tandem mass spectrometry and matrix-assisted laser desorption/ionization mass spectrometry. © 2014 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.


PubMed | Merck Stiftungsprofessur fur Molekulare Biotechnologie
Type: Journal Article | Journal: Chembiochem : a European journal of chemical biology | Year: 2013

Let it shine: The biosynthesis of the UV fluorophore legioliulin (1) from Legionella spp. was elucidated and the phenylalanine ammonium lyase LglD responsible for the formation of the starter unit cinnamic acid was biochemically characterized. Additionally, two novel derivatives differing in the starter unit have been identified by mutasynthesis experiments.


PubMed | Merck Stiftungsprofessur fur Molekulare Biotechnologie
Type: Journal Article | Journal: Chembiochem : a European journal of chemical biology | Year: 2014

The structure of the fabclavines-unique mixtures of nonribosomally derived peptide-polyketide hybrids connected to an unusual polyamino moiety-has been solved by detailed NMR and MS methods. These compounds have been identified in two different entomopathogenic Xenorhabdus strains, thereby leading also to the identification of the fabclavine biosynthesis gene cluster. Detailed analysis of these clusters and initial mutagenesis experiments allowed the prediction of a biosynthesis pathway in which the polyamino moiety is derived from an unusual type of fatty acid synthase that is normally involved in formation of polyunsaturated fatty acids. As fabclavines show broad-spectrum activity against bacteria, fungi, and other eukaryotic cells, they might act as protection factors against all kinds of food competitors during the complex life cycle of Xenorhabdus, its nematode host, and their insect prey.

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