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

Kunze, Brigitte; Reichenbach, Hans; Müller, Rolf; Höfle, Gerhard

doi:10.1038/ja.2005.28

Cited by 71 publications

(50 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The antimicrobial spectrum of 1 was determined by an agar-plate diffusion assay using paper discs as described previously [25]. The minimal inhibitory concentrations were determined with the conventional serial two-fold dilution method.…”

Section: Biological Activitymentioning

confidence: 99%

Pedein A and B: Production, Isolation, Structure Elucidation and Biological Properties of New Antifungal Cyclopeptides from Chondromyces pediculatus (Myxobacteria)

et al. 2008

Self Cite

View full text Add to dashboard Cite

Two new secondary metabolites, named pedein A and B, were isolated from the cell mass of the myxobacterium Chondromyces pediculatus. Their planar structures were elucidated by spectroscopic methods, in particular 2D NMR as 24-membered cyclic hexapeptides composed of a variable tryptophan residue, glycine, sarcosine and three unusual hydroxy b-and g-amino acids. The main component, pedein A, strongly inhibited the growth of yeasts and fungi, induced hemolysis of erythrocytes, and caused changes in membrane permeability of Rhodotorula glutinis. The structures of the pedeins are closely related to the large family of the microsclerodermins, which have been isolated from lithistid sponges of Microscleroderma and Theonella species. Keywords myxobacteria, pedeins, cyclic peptides, antifungal IntroductionMyxobacteria of the genus Chondromyces, suborder Sorangineae, have been shown to produce a variety of novel biologically active substances with different mechanisms of action. Thus, chondramides are inhibitors of the actin skeleton [1ϳ3], crocacin and ajudazols are mitochondrial electron transport inhibitors at different sites [4ϳ7], and apicularens are specific inhibitors of V-ATPase [8ϳ10]. Extracts of Chondromyces pediculatus, strain Cm p3 were noticed for their marked antifungal activity. HPLC/DAD/MS analysis of the extracts indicated the presence of six major components with molecular weights in the range of 781 to 924 mu of which two were correlated with the antifungal activity. The compounds responsible were isolated by column chromatography of the cell extract and named pedein A (1) and B (2). A tentative structure of 1 was depicted in the GBF Scientific Annual Report 1993 and at the international conference of microbial secondary metabolism in Interlaken 1994 [11] anticipating the structures of the related microsclerodermins [12ϳ14]. Here we describe in detail production, isolation, physicochemical properties and structure elucidation of 1 and 2 as well as biological properties of 1. Results Production and IsolationIn order to obtain smooth growth and reasonable cell densities, the producing organism had to be adapted to growth in liquid media by 4 to 8 transfers in shaken cultures. After that, the strain could be cultivated also in media based on technical substrates, e.g., Probion (single cell protein prepared from Methylomonas clarae; Hoechst AG, Frankfurt), soy flour, or oatmeal. effect of various technical substrates on the yields of 1 in 100-ml shake cultures of Chondromyces pediculatus strain Cm p3. By increasing the concentration of the technical substrates from 0.4 to 0.9% the amount of 1 usually decreased, with the exception of oatmeal, in which 1 production increased up to 11.9 mg/liter.The production of pedeins on a larger scale was performed in bioreactors containing media on the basis of different technical substrates. Yet comparable amounts of 1 as produced by cultivating strain Cm p3 in shake cultures, could not be achieved. In a 65-liter fermentation batch described in the experiment...

show abstract

Section: Biological Activitymentioning

confidence: 99%

Pedein A and B: Production, Isolation, Structure Elucidation and Biological Properties of New Antifungal Cyclopeptides from Chondromyces pediculatus (Myxobacteria)

et al. 2008

Self Cite

View full text Add to dashboard Cite

show abstract

“…The antimicrobial spectrum of cruentarens A and B was determined by an agar-plate diffusion assay using paper discs as described previously [12]. The minimal inhibition concentrations were determined with the serial two-fold dilution method.…”

Section: Biological Spectrummentioning

confidence: 99%

Cruentaren, a New Antifungal Salicylate-Type Macrolide from Byssovorax cruenta (Myxobacteria) with Inhibitory Effect on Mitochondrial ATPase Activity

et al. 2006

Self Cite

View full text Add to dashboard Cite

The novel macrolide cruentaren A was produced at levels up to 3.2 mg/liter by cultures of the myxobacterium Byssovorax cruenta. The new compound strongly inhibited the growth of yeasts and filamentous fungi and showed high cytotoxicity against L929 mouse fibroblast cells. A minor co-metabolite of cruentaren A, named cruentaren B, and identified as a six-membered lactone isomer of cruentaren A, showed only marginal cytotoxicity and no antifungal activity. Cruentaren A inhibited F 0 F 1 mitochondrial ATP-hydrolysis in submitochondrial particles of yeasts and beef heart.

show abstract

“…Besides being important intermediates in the degradation of these abundant amino acids, the thioesters are important starting units in the biosynthesis of secondary metabolites and fatty acids (FAs). Well-known examples for IB-CoA-or 2MB-CoA-primed secondary metabolites are the avermectins (8), but there are also several secondary metabolites that use IV-CoA as a starting unit (e.g., myxothiazol [24] and aurafuron [15]). In FA biosynthesis, IV-CoA, IB-CoA, and 2MB-CoA are the starting units of iso-odd, iso-even, and ante-iso-odd FAs, respectively, which can be found in various bacteria and can substitute for unsaturated fatty acids to maintain membrane fluidity at different temperatures (12).…”

mentioning

confidence: 99%

3-Hydroxy-3-Methylglutaryl-Coenzyme A (CoA) Synthase Is Involved in Biosynthesis of Isovaleryl-CoA in the Myxobacterium Myxococcus xanthus during Fruiting Body Formation

et al. 2006

View full text Add to dashboard Cite

Isovaleryl-coenzyme A (IV-CoA) is the starting unit for some secondary metabolites and iso-odd fatty acids in several bacteria. According to textbook biochemistry, IV-CoA is derived from leucine degradation, but recently an alternative pathway that branches from the well-known mevalonate-dependent isoprenoid biosynthesis has been described for myxobacteria. A double mutant was constructed in Myxococcus xanthus by deletion of genes involved in leucine degradation and disruption of mvaS encoding the 3-hydroxy-3-methylglutarylcoenzyme A synthase. A dramatic decrease of IV-CoA-derived iso-odd fatty acids was observed for the mutant, confirming mvaS to be involved in the alternative pathway. Additional quantitative real-time reverse transcription-PCR experiments indicated that mvaS is transcriptionally regulated by isovalerate. Furthermore, feeding studies employing an intermediate specific for the alternative pathway revealed that this pathway is induced during fruiting body formation, which presumably increases the amount of IV-CoA available when leucine is limited.

show abstract

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

Cited by 71 publications

References 31 publications

Pedein A and B: Production, Isolation, Structure Elucidation and Biological Properties of New Antifungal Cyclopeptides from Chondromyces pediculatus (Myxobacteria)

Pedein A and B: Production, Isolation, Structure Elucidation and Biological Properties of New Antifungal Cyclopeptides from Chondromyces pediculatus (Myxobacteria)

Cruentaren, a New Antifungal Salicylate-Type Macrolide from Byssovorax cruenta (Myxobacteria) with Inhibitory Effect on Mitochondrial ATPase Activity

3-Hydroxy-3-Methylglutaryl-Coenzyme A (CoA) Synthase Is Involved in Biosynthesis of Isovaleryl-CoA in the Myxobacterium Myxococcus xanthus during Fruiting Body Formation

Contact Info

Product

Resources

About