Antibiotika aus Gleitenden Bakterien, XV. Myaxalamide A, B, C und D eine Gruppe homologer Antibiotika aus <i>Myxococcus xanthus</i> Mx x12 (Myxobacterales)

Jansen, Rolf; Reifenstahl, Günther; Gerth, Klaus; Reichenbach, Hans; Höfle, Gerhard

doi:10.1002/jlac.198319830702

Cited by 49 publications

(30 citation statements)

References 18 publications

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“…Only L-malic acid was detected by chiral GC analysis. The relative anti configuration at C-12 and C-13 follows from the vicinal coupling of the respective protons by 8.3 Hz as it was observed with myxalamids [10].…”

Section: Physico-chemical Properties and Structurementioning

confidence: 54%

“…For example S. aurantiaca strain DW4/3-1 simultaneously produces the electron transport inhibitor myxothiazol [1], the dawenols [2], the myxochromides [3], and the iron chelators myxochelin A and B [4,5]. In culture extracts of S. aurantiaca, strain Sg a15 even five structurally entirely different groups of metabolites have been discovered, namely the inhibitors of the eukaryotic electron transport, the aurachins [6], stigmatellins [7,8], and myxalamids [7,9,10], and as in strain DW4/3-1 also the myxochelins [5] and minor amounts of myxochromides components [3]. Recently by genetic studies a variety of typical secondary metabolic gene clusters encoding multimodular polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS) have been identified in both S. aurantiaca, DW4/3-1 [3,11,12], and S. aurantiaca, Sg a15 [5, 13ϳ16].…”

Section: Introductionmentioning

confidence: 99%

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Aurafuron A and B, New Bioactive Polyketides from Stigmatella aurantiaca and Archangium gephyra (Myxobacteria)

et al. 2005

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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.

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Section: Physico-chemical Properties and Structurementioning

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Aurafuron A and B, New Bioactive Polyketides from Stigmatella aurantiaca and Archangium gephyra (Myxobacteria)

et al. 2005

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“…An impressive 37 additional compounds that represent putative novel metabolites could be defined. Some of these compounds may represent novel derivatives of previously classified natural product families, as families such as the DKxanthenes and the myxalamids occur in at least 11 and 4 slightly differing chemical forms, respectively (13,18).…”

Section: Discussionmentioning

confidence: 99%

“…M. xanthus strain DK1622 is the genotype most commonly studied with respect to social interactions and development. This strain has been found to produce several secondary metabolites, including the myxochromids (27), myxalamids (13), the antibiotic myxovirescin (8), and the siderophore myxochelin (15) (Fig. 1A).…”

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confidence: 99%

Discovering the Hidden Secondary Metabolome of Myxococcus xanthus : a Study of Intraspecific Diversity

Krug

Zurek

Revermann

et al. 2008

Appl Environ Microbiol

138

123

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As a monophyletic group, the myxobacteria are known to produce a broad spectrum of secondary metabolites. However, the degree of metabolic diversity that can be found within a single species remains unexplored. The model species Myxococcus xanthus produces several metabolites also present in other myxobacterial species, but only one compound unique to M. xanthus has been found to date. Here, we compare the metabolite profiles of 98 M. xanthus strains that originate from 78 locations worldwide and include 20 centimeter-scale isolates from one location. This screen reveals a strikingly high level of intraspecific diversity in the M. xanthus secondary metabolome. The identification of 37 nonubiquitous candidate compounds greatly exceeds the small number of secondary metabolites previously known to derive from this species. These results suggest that M. xanthus may be a promising source of future natural products and that thorough intraspecific screens of other species could reveal many new compounds of interest.Prokaryotes continue to provide important leads in the search for medically important bioactive natural products (1, 11). In particular, the myxobacteria have emerged as a promising source of natural products that exhibit highly diverse structures and biological activities (9). While most myxobacterial genera produce secondary metabolites, difficulties with cultivation and genetic manipulation hinder exploitation of the biosynthetic potential of many species. In contrast, the relatively fast growth and extensive genetic characterization of Myxococcus xanthus make the identification of natural products in this model species of particular interest.Myxococcus xanthus has been thoroughly investigated due to its amazing social behaviors, which include coordinated swarming over surfaces and a complex life cycle that culminates in the formation of multicellular fruiting bodies under starvation conditions (23). However, little attention has been paid to secondary metabolite production in this model species. M. xanthus strain DK1622 is the genotype most commonly studied with respect to social interactions and development. This strain has been found to produce several secondary metabolites, including the myxochromids (27), myxalamids (13), the antibiotic myxovirescin (8), and the siderophore myxochelin (15) (Fig. 1A). The molecular basis of synthesis for these compounds has been studied in some detail (25,26,30) and has been greatly facilitated by the availability of the DK1622 genome sequence (10). Very recently, a novel secondary metabolite class unique to M. xanthus, the DKxanthenes, was characterized and was shown to be essential for viable-spore formation (18). Additional reports of secondary metabolites from M. xanthus are limited to cittilin (20) and the antibiotics saframycin (12) and althiomycin (16).Most of these M. xanthus compounds are polyketides or nonribosomal peptides or hybrids thereof, and their biosynthesis is accomplished by large multienzyme complexes, the polyketide synthases (PKSs) or the nonri...

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“…Examples of polyketides with a branched chain carboxylic acid starter moiety are the anthelmintic agent avermectin produced by Streptomyces avermitilis (4), the clinically used virginiamycin group of antibiotics, and the electron transport inhibitors myxothiazol (5, 6) (compare Fig. 4) and myxalamid (7,8) from the myxobacterium Stigmatella aurantiaca. During our studies on the biosynthesis of the latter secondary metabolites in myxobacteria, we became interested in the Bkd locus of S. aurantiaca DW4/3-1, because it seems to regulate the production of starter molecules for primary metabolism (iso-FA) and secondary metabolism.…”

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confidence: 99%

A Novel Biosynthetic Pathway Providing Precursors for Fatty Acid Biosynthesis and Secondary Metabolite Formation in Myxobacteria

Mahmud

Bode

Silakowski

et al. 2002

Journal of Biological Chemistry

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Short chain carboxylic acids are well known as the precursors of fatty acid and polyketide biosynthesis. Iso-fatty acids, which are important for the control of membrane fluidity, are formed from branched chain starter units (isovaleryl-CoA and isobutyryl-CoA), which in turn are derived from the degradation of leucine and valine, respectively. Branched chain carboxylic acids are also employed as starter molecules for the biosynthesis of secondary metabolites, e.g. the therapeutically important anthelmintic agent avermectin or the electron transport inhibitor myxothiazol. During our studies on myxothiazol biosynthesis in the myxobacterium, Stigmatella aurantiaca, we detected a novel biosynthetic route to isovaleric acid. After cloning and inactivation of the branched chain keto acid dehydrogenase complex, which is responsible for the degradation of branched chain amino acids, the strain is still able to produce iso-fatty acids and myxothiazol. Incorporation studies employing deuterated leucine show that it can only serve as precursor in the wild type strain but not in the esg mutant. Feeding experiments using 13 C-labeled precursors show that isovalerate is efficiently made from acetate, giving rise to a labeling pattern in myxothiazol that provides evidence for a novel branch of the mevalonate pathway involving the intermediate 3,3-dimethylacryloyl-CoA. 3,3-Dimethylacrylic acid was synthesized in deuterated form and fed to the esg mutant, resulting in strong incorporation into myxothiazol and iso-fatty acids. Similar experiments employing Myxococcus xanthus revealed that the discovered biosynthetic route described is present in other myxobacteria as well.Fatty acids (FA) 1 are important building blocks of cell membranes. The various groups of prokaryotes differ remarkably in the structure and synthesis of fatty acid-derived lipids, which serve as reliable systematic marker molecules in chemotaxonomy (1). Unsaturated and branched chain (or iso-) FA increase the fluidity of the membrane and fulfill the function of thermal adaptation. The higher the content of these FA, the lower is the solid-to-liquid phase transition temperature of lipids.The biosynthesis of FA has been elucidated in detail, revealing that the difference between the biosynthetic pathways to FA and iso-FA lies only in the respective acylated primer acyl carrier proteins and in the condensing enzymes, which prefer modified primer acyl chains for elongation instead of the "normal" acetyl primer (1, 2). The modified primers used for iso-FA biosynthesis are the coenzyme A esters of isovaleric acid (IVA, resulting in iso-odd FA with an uneven number of carbon atoms), isobutyric acid (IBA, resulting in iso-even FA with an even number of carbon atoms), or 2-methyl butyric acid (2MBA, resulting in ante-iso FA, in which the methyl branch is located on the third carbon atom counted from the -end of the chain), which can be generated via the degradation pathway from branched chain amino acids or from intermediates of the biosyntheses of these essential amino...

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Antibiotika aus Gleitenden Bakterien, XV. Myaxalamide A, B, C und D eine Gruppe homologer Antibiotika aus Myxococcus xanthus Mx x12 (Myxobacterales)

Cited by 49 publications

References 18 publications

Aurafuron A and B, New Bioactive Polyketides from Stigmatella aurantiaca and Archangium gephyra (Myxobacteria)

Aurafuron A and B, New Bioactive Polyketides from Stigmatella aurantiaca and Archangium gephyra (Myxobacteria)

Discovering the Hidden Secondary Metabolome of Myxococcus xanthus : a Study of Intraspecific Diversity

A Novel Biosynthetic Pathway Providing Precursors for Fatty Acid Biosynthesis and Secondary Metabolite Formation in Myxobacteria

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