The Experts below are selected from a list of 261 Experts worldwide ranked by ideXlab platform
Rolf Müller - One of the best experts on this subject based on the ideXlab platform.
-
Novel features in a combined polyketide synthase/non-ribosomal peptide synthetase: the myxalamid biosynthetic gene cluster of the myxobacterium Stigmatella aurantiaca Sga15
Chemistry & Biology, 2020Co-Authors: Barbara Silakowski, Brigitte Kunze, Gabriele Nordsiek, Helmut Blocker, Rolf MüllerAbstract:Abstract Background : Myxobacteria have been well established as a potent source for natural products with biological activity. They produce a considerable variety of compounds which represent typical polyketide structures with incorporated amino acids (e.g. the epothilons, the myxothiazols and the myxalamids). Several of these secondary metabolites are effective inhibitors of the electron transport via the respiratory chain and have been widely used. Molecular cloning and characterization of the genes governing the biosynthesis of these structures is of considerable interest, because such information adds to the limited knowledge as to how polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) interact and how they might be manipulated in order to form novel antibiotics. Results : A DNA region of approximately 50 000 base pairs from Stigmatella aurantiaca Sga15 was sequenced and shown by gene disruption to be involved in myxalamid biosynthesis. Sequence analysis reveals that the myxalamids are formed by a combined PKS/NRPS system. The terminal NRPS MxaA extends the assembled polyketide chain of the myxalamids with alanine. MxaA contains an N-terminal domain with homology to NAD binding proteins, which is responsible during the biogenesis for a novel type of reductive chain release giving rise to the 2-amino-propanol moiety of the myxalamids. The last module of the PKS reveals an unprecedented genetic organization; it is encoded on two genes ( mxaB1 and mxaB2 ), subdividing the domains of one module from each other. A sequence comparison of myxobacterial acyl-transferase domains with known systems from streptomycetes and bacilli reveals that consensus sequences proposed to be specific for methylmalonyl-CoA and malonyl-CoA are not always reliable. Conclusions : The complete biosynthetic gene cluster of the myxalamid-type electron transport inhibitor from S. aurantiaca Sga15 has been cloned and analyzed. It represents one of the few examples of combined PKS/NRPS systems, the analysis and manipulation of which has the potential to generate novel hybrid structures via combinatorial biosynthesis (e.g. via module-swapping techniques). Additionally, a new type of reductive release from PKS/NRPS systems is described.
-
a highly unusual polyketide synthase directs dawenol polyene biosynthesis in Stigmatella aurantiaca
Journal of Biotechnology, 2014Co-Authors: Corina Oswald, Nestor Zaburannyi, Christian Burgard, Thomas Hoffmann, Silke C Wenzel, Rolf MüllerAbstract:Enormous progress in the field of polyketide biosynthesis has led to the establishment of rules for general text book biosynthetic logic and consequently to the assumption that biosynthetic genes can be easily correlated with the corresponding natural products. However, non-textbook examples of polyketide assembly continue to be discovered suggesting the gene to product and product to gene predictions need improvement, especially as they are increasingly used in the post-genomic era. Here, we analyzed the genomic blueprint of a myxobacterial multi-producer of secondary metabolites, Stigmatella aurantiaca DW4/3-1, for its biosynthetic potential by genome-mining. In addition to the five polyketide synthase and/or nonribosomal peptide synthetase gene clusters of known function we identified a further 13 genomic regions exemplifying the enormous genetic potential for the production of additional chemical diversity by this strain. We show by gene inactivation and heterologous expression of the newly identified biosynthetic pathway for dawenol that the biosynthesis of this known polyene does not follow text book biosynthetic logic. Intriguingly, a genomic locus encoding an unusual polyketide synthase exhibiting similarity to gene loci involved in the formation of polyunsaturated fatty acids and secondary lipids was identified.
-
discovery of the rhizopodin biosynthetic gene cluster in Stigmatella aurantiaca sg a15 by genome mining
ChemBioChem, 2012Co-Authors: Dominik Pistorius, Rolf MüllerAbstract:The field of bacterial natural product research is currently undergoing a paradigm change concerning the discovery of natural products. Previously most efforts were based on isolation of the most abundant compound in an extract, or on tracking bioactivity. However, traditional activity-guided approaches are limited by the available test panels and frequently lead to the rediscovery of already known compounds. The constantly increasing availability of bacterial genome sequences provides the potential for the discovery of a huge number of new natural compounds by in silico identification of biosynthetic gene clusters. Examination of the information on the biosynthetic machinery can further prevent rediscovery of known compounds, and can help identify so far unknown biosynthetic pathways of known compounds. By in silico screening of the genome of the myxobacterium Stigmatella aurantiaca Sg a15, a trans-AT polyketide synthase/non-ribosomal peptide synthetase (PKS/NRPS) gene cluster was identified that could not be correlated to any secondary metabolite known to be produced by this strain. Targeted gene inactivation and analysis of extracts from the resulting mutants by high performance liquid chromatography coupled to high resolution mass spectrometry (HPLC-HRMS), in combination with the use of statistical tools resulted in the identification of a compound that was absent in the mutants extracts. By matching with our in-house database of myxobacterial secondary metabolites, this compound was identified as rhizopodin. A detailed analysis of the rhizopodin biosynthetic machinery is presented in this manuscript.
-
auaa a membrane bound farnesyltransferase from Stigmatella aurantiaca catalyzes the prenylation of 2 methyl 4 hydroxyquinoline in the biosynthesis of aurachins
ChemBioChem, 2011Co-Authors: Edyta Stec, Rolf Müller, Dominik Pistorius, Shuming LiAbstract:Aurachins are quinoline alkaloids isolated from the myxobacterium Stigmatella aurantiaca. They are substituted with an isoprenoid side chain and act as potent inhibitors in the electron transport chain. A biosynthetic gene cluster that contains at least five genes (auaA–auaE) has been identified for aurachin biosynthesis. In this study, auaA, the gene encoding a putative prenyltransferase of 326 amino acids, was cloned and overexpressed in Escherichia coli. Biochemical investigations showed that AuaA catalyzes the prenylation of 2-methyl-4-hydroxyquinoline in the presence of farnesyl diphosphate (FPP), thereby resulting in the formation of aurachin D. The hydroxyl group at position C4 of the quinoline ring is essential for an acceptance by AuaA; this was concluded by testing 18 quinoline derivatives or analogues with AuaA and FPP. 1H NMR and HR-EI-MS analyses of six isolated enzyme products revealed the presence of a farnesyl moiety at position C3 of the quinoline ring. KM values of 43 and 270 μM were determined for FPP and 2-methyl-4-hydroxyquinoline, respectively. Like other known membrane-bound prenyltransferases, the reaction catalyzed by AuaA is dependent on the presence of metal ions such as Mg2+, Mn2+ and Co2+, although no typical (N/D)DXXD binding motif was found in the sequence.
-
Investigation of cytochromes P450 in myxobacteria: Excavation of cytochromes P450 from the genome of Sorangium cellulosum So ce56
FEBS Letters, 2011Co-Authors: Yogan Khatri, Rolf Müller, Frank Hannemann, Olena Perlova, Rita BernhardtAbstract:The exploitation of cytochromes P450 for novel biotechnological application and for the investigation of their physiological function is of great scientific interest in this post genomic era, where an extraordinary biodiversity of P450 genes has been derived from all forms of life. The study of P450s in the myxobacterium Sorangium cellulosum strain So ce56, the producer of novel secondary metabolites of pharmaceutical interest is the research topic, in which we were engaged since the beginning of its genome sequencing project. We herein disclosed the cytochrome P450 complements (CYPomes) of spore-forming myxobacterial species, Stigmatella aurantiaca DW4/3-1, Haliangium ochraceum DSM 14365 and Myxococcus xanthus DK1622, and their potential pharmaceutical significance has been discussed.
Hans Ulrich Schairer - One of the best experts on this subject based on the ideXlab platform.
-
integration into the phage attachment site attb impairs multicellular differentiation in Stigmatella aurantiaca
Journal of Bacteriology, 2006Co-Authors: Hans Ulrich Schairer, Susanne Muller, Hui Shen, Diana Hofmann, John R KirbyAbstract:Stigmatella aurantiaca displays a complex developmental life cycle in response to starvation conditions that results in the formation of tree-like fruiting bodies capable of producing spores. The phage Mx8, first isolated from the close relative Myxococcus xanthus, is unable to infect S. aurantiaca cells and integrate into the genome. However, plasmids containing Mx8 fragments encoding the integrase and attP are able to integrate at the attB locus in the S. aurantiaca genome by site-specific recombination. After recombination between attP and attB, the S. aurantiaca cells were incapable of building normal fruiting bodies but formed clumps and fungus-like structures characteristic of intermediate stages of development displayed by the wild type. We identified two tRNA genes, trnD and trnV, encoding tRNAAsp and tRNAVal, respectively, composing an operon at the attB locus of S. aurantiaca. Integration of attP-containing plasmids resulted in the incorporation of the tMx8 terminator sequence, in addition to a short sequence of Mx8 DNA downstream of trnD. The integrant was unable to process the trnD transcript at the normal 3′ processing site and displayed a lower level of expression of the trnVD operon. In addition, several developmentally regulated proteins were no longer produced in mutants following insertion at the attB locus. We hypothesize that the integration of the tMx8 terminator sequence results in reduced levels of mature tRNAAsp and tRNAVal and that altered protein production during development is thereby responsible for the observed phenotype. The trnVD locus thus defines a new developmental checkpoint for Stigmatella aurantiaca.
-
sigb an alternative sigma factor of the myxobacterium Stigmatella aurantiaca is synthesized during development and heat shock
Microbiology, 2001Co-Authors: Barbara Silakowski, Susanne Muller, H Skladny, Heidi Ehret, Hans Ulrich SchairerAbstract:Alternative sigma factors have been detected in the myxobacterium Stigmatella aurantiaca during indole-induced sporulation, fruiting body formation and heat shock using an antiserum raised against sigma factor SigB. The time course of sigB gene expression was analysed by RT-PCR and by determining β-galactosidase activity during development in a merodiploid strain that harboured a sigB–lacZ fusion gene. Inactivation of the sigB gene by insertion of the neo gene resulted in the loss of one sigma factor as shown by Western analysis. Neither fruiting body formation nor sporulation, nor the production of possible SigB targets, such as DnaK, GroEL or HspA, were affected.
-
new lessons for combinatorial biosynthesis from myxobacteria the myxothiazol biosynthetic gene cluster of Stigmatella aurantiaca dw4 3 1
Journal of Biological Chemistry, 1999Co-Authors: Barbara Silakowski, Hans Ulrich Schairer, Brigitte Kunze, Gerhard Hofle, Heidi Ehret, Gabriele Nordsiek, Helmut Blocker, Stefan Weinig, Petra Brandt, Stefan BeyerAbstract:Abstract The biosynthetic mta gene cluster responsible for myxothiazol formation from the fruiting body forming myxobacterium Stigmatella aurantiaca DW4/3-1 was sequenced and analyzed. Myxothiazol, an inhibitor of the electron transport via the bc 1-complex of the respiratory chain, is biosynthesized by a unique combination of several polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS), which are activated by the 4′-phosphopantetheinyl transferase MtaA. Genomic replacement of a fragment of mtaB and insertion of a kanamycin resistance gene into mtaA both impaired myxothiazol synthesis. Genes mtaC and mtaDencode the enzymes for bis-thiazol(ine) formation and chain extension on one pure NRPS (MtaC) and on a unique combination of PKS and NRPS (MtaD). The genes mtaE and mtaF encode PKSs including peptide fragments with homology to methyltransferases. These methyltransferase modules are assumed to be necessary for the formation of the proposed methoxy- and β-methoxy-acrylate intermediates of myxothiazol biosynthesis. The last gene of the cluster,mtaG, again resembles a NRPS and provides insight into the mechanism of the formation of the terminal amide of myxothiazol. The carbon backbone of an amino acid added to the myxothiazol-acid is assumed to be removed via an unprecedented module with homology to monooxygenases within MtaG.
-
intercellular signalling in Stigmatella aurantiaca
Current Opinion in Microbiology, 1999Co-Authors: Wulf Plaga, Hans Ulrich SchairerAbstract:Abstract The myxobacterium Stigmatella aurantiaca is a prokaryotic model used to study intercellular signalling and the genetic determination of morphogenesis. Signalling factors and genes required for the generation of the elaborate multicellular fruiting body are to be identified. Recently, the structure of stigmolone, which is the pheromone necessary for fruiting body formation, was elucidated, and genes involved in development were characterised. Progress has also been made in the genetic accessibility of S. aurantiaca.
-
intercellular signaling in Stigmatella aurantiaca purification and characterization of stigmolone a myxobacterial pheromone
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Wulf Plaga, Irmela Stamm, Hans Ulrich SchairerAbstract:The myxobacterium Stigmatella aurantiaca passes through a life cycle that involves formation of a multicellular fruiting body as the most complex stage. An early step in this differentiation process depends on a signal factor secreted by the cells when nutrients become limited. The formation of a fruiting body from a small cell population can be accelerated by addition of this secreted material. The bioactive compound was found to be steam volatile. It was purified to homogeneity by steam distillation followed by reversed-phase and normal-phase HPLC. The pheromone was named stigmolone, in accordance with the structure 2,5,8-trimethyl-8-hydroxy-nonan-4-one, as determined by NMR and mass spectrometry. Stigmolone represents a structurally unique and highly bioactive prokaryotic pheromone that is effective in the bioassay at 1 nM concentration.
Barbara Silakowski - One of the best experts on this subject based on the ideXlab platform.
-
SigB, an alternative sigma factor of the myxobacterium Stigmatella aurantiaca, is synthesized during development and heat shock.
Microbiology (Reading England), 2020Co-Authors: Barbara Silakowski, Susanne Muller, Heidi Ehret, Heyko Skladny, Hans U SchairerAbstract:Alternative sigma factors have been detected in the myxobacterium Stigmatella aurantiaca during indole-induced sporulation, fruiting body formation and heat shock using an antiserum raised against sigma factor SigB. The time course of sigB gene expression was analysed by RT-PCR and by determining beta-galactosidase activity during development in a merodiploid strain that harboured a sigB-lacZ fusion gene. Inactivation of the sigB gene by insertion of the neo gene resulted in the loss of one sigma factor as shown by Western analysis. Neither fruiting body formation nor sporulation, nor the production of possible SigB targets, such as DnaK, GroEL or HspA, were affected.
-
Novel features in a combined polyketide synthase/non-ribosomal peptide synthetase: the myxalamid biosynthetic gene cluster of the myxobacterium Stigmatella aurantiaca Sga15
Chemistry & Biology, 2020Co-Authors: Barbara Silakowski, Brigitte Kunze, Gabriele Nordsiek, Helmut Blocker, Rolf MüllerAbstract:Abstract Background : Myxobacteria have been well established as a potent source for natural products with biological activity. They produce a considerable variety of compounds which represent typical polyketide structures with incorporated amino acids (e.g. the epothilons, the myxothiazols and the myxalamids). Several of these secondary metabolites are effective inhibitors of the electron transport via the respiratory chain and have been widely used. Molecular cloning and characterization of the genes governing the biosynthesis of these structures is of considerable interest, because such information adds to the limited knowledge as to how polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) interact and how they might be manipulated in order to form novel antibiotics. Results : A DNA region of approximately 50 000 base pairs from Stigmatella aurantiaca Sga15 was sequenced and shown by gene disruption to be involved in myxalamid biosynthesis. Sequence analysis reveals that the myxalamids are formed by a combined PKS/NRPS system. The terminal NRPS MxaA extends the assembled polyketide chain of the myxalamids with alanine. MxaA contains an N-terminal domain with homology to NAD binding proteins, which is responsible during the biogenesis for a novel type of reductive chain release giving rise to the 2-amino-propanol moiety of the myxalamids. The last module of the PKS reveals an unprecedented genetic organization; it is encoded on two genes ( mxaB1 and mxaB2 ), subdividing the domains of one module from each other. A sequence comparison of myxobacterial acyl-transferase domains with known systems from streptomycetes and bacilli reveals that consensus sequences proposed to be specific for methylmalonyl-CoA and malonyl-CoA are not always reliable. Conclusions : The complete biosynthetic gene cluster of the myxalamid-type electron transport inhibitor from S. aurantiaca Sga15 has been cloned and analyzed. It represents one of the few examples of combined PKS/NRPS systems, the analysis and manipulation of which has the potential to generate novel hybrid structures via combinatorial biosynthesis (e.g. via module-swapping techniques). Additionally, a new type of reductive release from PKS/NRPS systems is described.
-
structure and biosynthesis of myxochromides s1 3 in Stigmatella aurantiaca evidence for an iterative bacterial type i polyketide synthase and for module skipping in nonribosomal peptide biosynthesis
ChemBioChem, 2005Co-Authors: Silke C Wenzel, Brigitte Kunze, Gerhard Hofle, Barbara Silakowski, Helmut Blocker, Maren Scharfe, Rolf MüllerAbstract:The myxobacterium Stigmatella aurantiaca DW4/3-1 harbours an astonishing variety of secondary metabolic gene clusters, at least two of which were found by gene inactivation experiments to be connected to the biosynthesis of previously unknown metabolites. In this study, we elucidate the structures of myxochromides S1-3, novel cyclic pentapeptide natural products possessing unsaturated polyketide side chains, and identify the corresponding biosynthetic gene locus, made up of six nonribosomal peptide synthetase modules. By analyzing the deduced substrate specificities of the adenylation domains, it is shown that module 4 is most probably skipped during the biosynthetic process. The polyketide synthase MchA harbours only one module and is presumably responsible for the formation of the variable complete polyketide side chains. These data indicate that MchA is responsible for an unusual iterative polyketide chain assembly.
-
Structure and Biosynthesis of Myxochromides S1–3 in Stigmatella aurantiaca: Evidence for an Iterative Bacterial Type I Polyketide Synthase and for Module Skipping in Nonribosomal Peptide Biosynthesis
ChemBioChem, 2005Co-Authors: Silke C Wenzel, Brigitte Kunze, Gerhard Hofle, Barbara Silakowski, Helmut Blocker, Maren Scharfe, Rolf MüllerAbstract:The myxobacterium Stigmatella aurantiaca DW4/3-1 harbours an astonishing variety of secondary metabolic gene clusters, at least two of which were found by gene inactivation experiments to be connected to the biosynthesis of previously unknown metabolites. In this study, we elucidate the structures of myxochromides S1-3, novel cyclic pentapeptide natural products possessing unsaturated polyketide side chains, and identify the corresponding biosynthetic gene locus, made up of six nonribosomal peptide synthetase modules. By analyzing the deduced substrate specificities of the adenylation domains, it is shown that module 4 is most probably skipped during the biosynthetic process. The polyketide synthase MchA harbours only one module and is presumably responsible for the formation of the variable complete polyketide side chains. These data indicate that MchA is responsible for an unusual iterative polyketide chain assembly.
-
Steroid biosynthesis in prokaryotes: identification of myxobacterial steroids and cloning of the first bacterial 2,3(S)‐oxidosqualene cyclase from the myxobacterium Stigmatella aurantiaca
Molecular Microbiology, 2003Co-Authors: Helge B Bode, Hans Reichenbach, Barbara Silakowski, Silke C Wenzel, Bernd Zeggel, Rolf MüllerAbstract:Summary Steroids, such as cholesterol, are synthesized in almost all eukaryotic cells, which use these triterpenoid lipids to control the fluidity and flexibility of their cell membranes. Bacteria rarely synthesize such tetracyclic compounds but frequently replace them with a different class of triterpenoids, the pentacyclic hopanoids. The intriguing mechanisms involved in triterpene biosynthesis have attracted much attention, resulting in extensive studies of squalene-hopene cyclase in bacteria and (S)-2,3-oxidosqualene cyclases in eukarya. Nevertheless, almost nothing is known about steroid biosynthesis in bacteria. Only three steroid-synthesizing bacterial species have been identified before this study. Here, we report on a variety of sterol-producing myxobacteria. Stigmatella aurantiaca is shown to produce cycloartenol, the well-known first cyclization product of steroid biosynthesis in plants and algae. Additionally, we describe the cloning of the first bacterial steroid biosynthesis gene, cas, encoding the cycloartenol synthase (Cas) of S. aurantiaca. Mutants of cas generated via site-directed mutagenesis do not produce the compound. They show neither growth retardation in comparison with wild type nor any increase in ethanol sensitivity. The protein encoded by cas is most similar to the Cas proteins from several plant species, indicating a close evolutionary relationship between myxobacterial and eukaryotic steroid biosynthesis.
Brigitte Kunze - One of the best experts on this subject based on the ideXlab platform.
-
Novel features in a combined polyketide synthase/non-ribosomal peptide synthetase: the myxalamid biosynthetic gene cluster of the myxobacterium Stigmatella aurantiaca Sga15
Chemistry & Biology, 2020Co-Authors: Barbara Silakowski, Brigitte Kunze, Gabriele Nordsiek, Helmut Blocker, Rolf MüllerAbstract:Abstract Background : Myxobacteria have been well established as a potent source for natural products with biological activity. They produce a considerable variety of compounds which represent typical polyketide structures with incorporated amino acids (e.g. the epothilons, the myxothiazols and the myxalamids). Several of these secondary metabolites are effective inhibitors of the electron transport via the respiratory chain and have been widely used. Molecular cloning and characterization of the genes governing the biosynthesis of these structures is of considerable interest, because such information adds to the limited knowledge as to how polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) interact and how they might be manipulated in order to form novel antibiotics. Results : A DNA region of approximately 50 000 base pairs from Stigmatella aurantiaca Sga15 was sequenced and shown by gene disruption to be involved in myxalamid biosynthesis. Sequence analysis reveals that the myxalamids are formed by a combined PKS/NRPS system. The terminal NRPS MxaA extends the assembled polyketide chain of the myxalamids with alanine. MxaA contains an N-terminal domain with homology to NAD binding proteins, which is responsible during the biogenesis for a novel type of reductive chain release giving rise to the 2-amino-propanol moiety of the myxalamids. The last module of the PKS reveals an unprecedented genetic organization; it is encoded on two genes ( mxaB1 and mxaB2 ), subdividing the domains of one module from each other. A sequence comparison of myxobacterial acyl-transferase domains with known systems from streptomycetes and bacilli reveals that consensus sequences proposed to be specific for methylmalonyl-CoA and malonyl-CoA are not always reliable. Conclusions : The complete biosynthetic gene cluster of the myxalamid-type electron transport inhibitor from S. aurantiaca Sga15 has been cloned and analyzed. It represents one of the few examples of combined PKS/NRPS systems, the analysis and manipulation of which has the potential to generate novel hybrid structures via combinatorial biosynthesis (e.g. via module-swapping techniques). Additionally, a new type of reductive release from PKS/NRPS systems is described.
-
biosynthesis of aurachins a l in Stigmatella aurantiaca a feeding study
Journal of Natural Products, 2008Co-Authors: Gerhard Hofle, Brigitte KunzeAbstract:The isolation of aurachins A−L (1−11) from Stigmatella aurantiaca strain Sg a15 is described. Their structures and relative configurations were deduced from spectroscopic data, in particular NMR. Three structural types were identified: A-type aurachins (1, 2, 6) are C-3 oxygen-substituted quinolines carrying a farnesyl residue on C-4, C-type aurachins (3, 4, 7−11) are C-4 oxygen-substituted quinolines carrying a farnesyl residue on C-3, and C-type aurachin E (5) has a [1,1a,8,d]imidazoloquinoline structure. Feeding of 13C-labeled precursors showed that the quinoline ring is constructed from anthranilic acid and acetate, and the farnesyl residue from acetate by both the mevalonate and nonmevalonate pathways. Further, feeding of labeled aurachin C (3) indicated the A-type aurachins are derived by a novel intramolecular 3,4-migration of the farnesyl residue that is induced by a 2,3-epoxidation and terminated by a reduction step. 18O-Labeling experiments indicated the new oxygen substituents originate from at...
-
aurafuron a and b new bioactive polyketides from Stigmatella aurantiaca and archangium gephyra myxobacteria fermentation isolation physico chemical properties structure and biological activity
The Journal of Antibiotics, 2005Co-Authors: Brigitte Kunze, Hans Reichenbach, Rolf Müller, Gerhard HofleAbstract:New antibiotic polyketides, named aurafuron A (1) and B (2) were isolated from culture extracts of myxobacteria of the species Stigmatella aurantiaca and Archangium gephyra, strain Ar 10844. By multi-step chromatography 1 and 2 were separated from a variety of other non-related co-metabolites, and their structures elucidated by spectroscopic methods as new 5-alkenyl-3 3(2H)-furanones. Aurafurons inhibited the growth of some filamentous fungi and additionally, aurafuron B was weakly active against few Gram-positive bacteria. Both compounds also showed cytotoxic activity against the mouse fibroblast cell line L929.
-
Aurafuron A and B, New Bioactive Polyketides from Stigmatella aurantiaca and Archangium gephyra (Myxobacteria)
The Journal of Antibiotics, 2005Co-Authors: Brigitte Kunze, Hans Reichenbach, Rolf Müller, Gerhard HofleAbstract:New antibiotic polyketides, named aurafuron A ( 1 ) and B ( 2 ) were isolated from culture extracts of myxobacteria of the species Stigmatella aurantiaca and Archangium gephyra , strain Ar 10844. By multi-step chromatography 1 and 2 were separated from a variety of other non-related co-metabolites, and their structures elucidated by spectroscopic methods as new 5-alkenyl-3 3(2 H )-furanones. Aurafurons inhibited the growth of some filamentous fungi and additionally, aurafuron B was weakly active against few Gram-positive bacteria. Both compounds also showed cytotoxic activity against the mouse fibroblast cell line L929.
-
structure and biosynthesis of myxochromides s1 3 in Stigmatella aurantiaca evidence for an iterative bacterial type i polyketide synthase and for module skipping in nonribosomal peptide biosynthesis
ChemBioChem, 2005Co-Authors: Silke C Wenzel, Brigitte Kunze, Gerhard Hofle, Barbara Silakowski, Helmut Blocker, Maren Scharfe, Rolf MüllerAbstract:The myxobacterium Stigmatella aurantiaca DW4/3-1 harbours an astonishing variety of secondary metabolic gene clusters, at least two of which were found by gene inactivation experiments to be connected to the biosynthesis of previously unknown metabolites. In this study, we elucidate the structures of myxochromides S1-3, novel cyclic pentapeptide natural products possessing unsaturated polyketide side chains, and identify the corresponding biosynthetic gene locus, made up of six nonribosomal peptide synthetase modules. By analyzing the deduced substrate specificities of the adenylation domains, it is shown that module 4 is most probably skipped during the biosynthetic process. The polyketide synthase MchA harbours only one module and is presumably responsible for the formation of the variable complete polyketide side chains. These data indicate that MchA is responsible for an unusual iterative polyketide chain assembly.
Gerhard Hofle - One of the best experts on this subject based on the ideXlab platform.
-
biosynthesis of aurachins a l in Stigmatella aurantiaca a feeding study
Journal of Natural Products, 2008Co-Authors: Gerhard Hofle, Brigitte KunzeAbstract:The isolation of aurachins A−L (1−11) from Stigmatella aurantiaca strain Sg a15 is described. Their structures and relative configurations were deduced from spectroscopic data, in particular NMR. Three structural types were identified: A-type aurachins (1, 2, 6) are C-3 oxygen-substituted quinolines carrying a farnesyl residue on C-4, C-type aurachins (3, 4, 7−11) are C-4 oxygen-substituted quinolines carrying a farnesyl residue on C-3, and C-type aurachin E (5) has a [1,1a,8,d]imidazoloquinoline structure. Feeding of 13C-labeled precursors showed that the quinoline ring is constructed from anthranilic acid and acetate, and the farnesyl residue from acetate by both the mevalonate and nonmevalonate pathways. Further, feeding of labeled aurachin C (3) indicated the A-type aurachins are derived by a novel intramolecular 3,4-migration of the farnesyl residue that is induced by a 2,3-epoxidation and terminated by a reduction step. 18O-Labeling experiments indicated the new oxygen substituents originate from at...
-
Aurafuron A and B, New Bioactive Polyketides from Stigmatella aurantiaca and Archangium gephyra (Myxobacteria)
The Journal of Antibiotics, 2005Co-Authors: Brigitte Kunze, Hans Reichenbach, Rolf Müller, Gerhard HofleAbstract:New antibiotic polyketides, named aurafuron A ( 1 ) and B ( 2 ) were isolated from culture extracts of myxobacteria of the species Stigmatella aurantiaca and Archangium gephyra , strain Ar 10844. By multi-step chromatography 1 and 2 were separated from a variety of other non-related co-metabolites, and their structures elucidated by spectroscopic methods as new 5-alkenyl-3 3(2 H )-furanones. Aurafurons inhibited the growth of some filamentous fungi and additionally, aurafuron B was weakly active against few Gram-positive bacteria. Both compounds also showed cytotoxic activity against the mouse fibroblast cell line L929.
-
aurafuron a and b new bioactive polyketides from Stigmatella aurantiaca and archangium gephyra myxobacteria fermentation isolation physico chemical properties structure and biological activity
The Journal of Antibiotics, 2005Co-Authors: Brigitte Kunze, Hans Reichenbach, Rolf Müller, Gerhard HofleAbstract:New antibiotic polyketides, named aurafuron A (1) and B (2) were isolated from culture extracts of myxobacteria of the species Stigmatella aurantiaca and Archangium gephyra, strain Ar 10844. By multi-step chromatography 1 and 2 were separated from a variety of other non-related co-metabolites, and their structures elucidated by spectroscopic methods as new 5-alkenyl-3 3(2H)-furanones. Aurafurons inhibited the growth of some filamentous fungi and additionally, aurafuron B was weakly active against few Gram-positive bacteria. Both compounds also showed cytotoxic activity against the mouse fibroblast cell line L929.
-
structure and biosynthesis of myxochromides s1 3 in Stigmatella aurantiaca evidence for an iterative bacterial type i polyketide synthase and for module skipping in nonribosomal peptide biosynthesis
ChemBioChem, 2005Co-Authors: Silke C Wenzel, Brigitte Kunze, Gerhard Hofle, Barbara Silakowski, Helmut Blocker, Maren Scharfe, Rolf MüllerAbstract:The myxobacterium Stigmatella aurantiaca DW4/3-1 harbours an astonishing variety of secondary metabolic gene clusters, at least two of which were found by gene inactivation experiments to be connected to the biosynthesis of previously unknown metabolites. In this study, we elucidate the structures of myxochromides S1-3, novel cyclic pentapeptide natural products possessing unsaturated polyketide side chains, and identify the corresponding biosynthetic gene locus, made up of six nonribosomal peptide synthetase modules. By analyzing the deduced substrate specificities of the adenylation domains, it is shown that module 4 is most probably skipped during the biosynthetic process. The polyketide synthase MchA harbours only one module and is presumably responsible for the formation of the variable complete polyketide side chains. These data indicate that MchA is responsible for an unusual iterative polyketide chain assembly.
-
Structure and Biosynthesis of Myxochromides S1–3 in Stigmatella aurantiaca: Evidence for an Iterative Bacterial Type I Polyketide Synthase and for Module Skipping in Nonribosomal Peptide Biosynthesis
ChemBioChem, 2005Co-Authors: Silke C Wenzel, Brigitte Kunze, Gerhard Hofle, Barbara Silakowski, Helmut Blocker, Maren Scharfe, Rolf MüllerAbstract:The myxobacterium Stigmatella aurantiaca DW4/3-1 harbours an astonishing variety of secondary metabolic gene clusters, at least two of which were found by gene inactivation experiments to be connected to the biosynthesis of previously unknown metabolites. In this study, we elucidate the structures of myxochromides S1-3, novel cyclic pentapeptide natural products possessing unsaturated polyketide side chains, and identify the corresponding biosynthetic gene locus, made up of six nonribosomal peptide synthetase modules. By analyzing the deduced substrate specificities of the adenylation domains, it is shown that module 4 is most probably skipped during the biosynthetic process. The polyketide synthase MchA harbours only one module and is presumably responsible for the formation of the variable complete polyketide side chains. These data indicate that MchA is responsible for an unusual iterative polyketide chain assembly.
