Disciformycins A and B: 12‐Membered Macrolide Glycoside Antibiotics from the Myxobacterium <i>Pyxidicoccus fallax</i> Active against Multiresistant Staphylococci

Surup, Frank; Viehrig, Konrad; Mohr, Kathrin I.; Herrmann, Jennifer; Jansen, Rolf; Müller, Rolf

doi:10.1002/anie.201406973

Cited by 50 publications

(46 citation statements)

References 32 publications

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“…6,7 An illustrative example is Pyxidicoccus fallax, which secretes diverse macrolide antibiotics, including the gulmirecins and the disciformycins. 8,9 Although the activity spectrum of these molecules correlates quite well with the bacterial prey spectrum of P. fallax, it does not explain the observed predation of eukaryotic microorganisms. In consideration of the metabolic versatility of myxobacteria, we hence decided to expand the bioactivity testing of the gulmirecinproducing P. fallax strain HKI 727 and to search for compounds with antiproliferative or cytotoxic effects.…”

mentioning

confidence: 92%

Myxochelins Target Human 5-Lipoxygenase

Schieferdecker¹,

König

Koeberle

et al. 2015

J. Nat. Prod.

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Extracts of the predatory myxobacterium Pyxidicoccus fallax HKI 727 showed antiproliferative effects on leukemic K-562 cells. Bioactivity-guided fractionation led to the isolation of the bis-catechol myxochelin A and two new congeners. The biosynthetic origin of myxochelins C and D was confirmed by feeding studies with isotopically labeled precursors. Pharmacological testing revealed human 5-lipoxygenase (5-LO) as a molecular target of the myxochelins. In particular, myxochelin A efficiently inhibited 5-LO activity with an IC50 of 1.9 μM and reduced the proliferation of K-562 cells at similar concentrations.

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mentioning

confidence: 92%

Myxochelins Target Human 5-Lipoxygenase

Schieferdecker¹,

König

Koeberle

et al. 2015

J. Nat. Prod.

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“…Beside their interesting life-style expressed by the development of often colorful fruiting bodies and dry resistant myxospores (Reichenbach & Dworkin, 1992), myxobacteria are extremely interesting with regard to their great potential to produce a high diversity of bioactive secondary metabolites (Weissman & Müller, 2010). To date more than 100 substances, many with promising antibiotic (Baumann et al, 2014;Surup et al, 2014), antiviral (Plaza et al, 2012), antifungal (Gerth, Bedorf, Irschik, Höfle, & Reichenbach, 1994), or anticancer activity (Gerth, Bedorf, Höfle, Irschik, & Reichenbach, 1996), could be isolated from myxobacteria and the limit has not been reached. Particularly in times of increasing antibiotic resistances the discovery and development of new antibiotics is of high importance.…”

Section: Introductionmentioning

confidence: 99%

Myxobacteria in high moor and fen: An astonishing diversity in a neglected extreme habitat

et al. 2017

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Increasing antibiotic resistances of numerous pathogens mean that myxobacteria, well known producers of new antibiotics, are becoming more and more interesting. More than 100 secondary metabolites, most of them with bioactivity, were described from the order Myxococcales. Especially new myxobacterial genera and species turned out to be reliable sources for novel antibiotics and can be isolated from uncommon neglected habitats like, for example, acidic soils. Almost nothing is known about the diversity of myxobacteria in moors, except some information from cultivation studies of the 1970s. Therefore, we evaluated the myxobacterial community composition of acidic high moor and fen both with cultivation‐independent 16S rRNA clone bank analysis and with cultivation. Phylogenetic analyses of clone sequences revealed a great potential of undescribed myxobacteria in high moor and fen, whereby all sequences represent unknown taxa and were detected exclusively by cultivation‐independent analyses. However, many clones were assigned to sequences from other cultivation‐independent studies of eubacterial diversity in acidic habitats. Cultivation revealed different strains exclusively from the genus Corallococcus. Our study shows that the neglected habitat moor is a promising source and of high interest with regard to the cultivation of prospective new bioactive secondary metabolite producing myxobacteria.

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“…Recently, a group of macrocyclic polyketides was independently reported by the groups of Müller and Nett , . Disciformycins A ( 1 ) and B ( 2 ) were isolated from Pyxidicoccus fallax AndGT8 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of the Aglycon of the Antibiotic Disciformycin

Wolling

Kirschning

2018

Eur J Org Chem

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The synthesis of the aglycon of disciformycin, a new secondary metabolite from Pyxidicoccus fallax, is reported. The disciformycins are highly potent antibiotics including inhibitory activity towards methicillin‐ and vancomycin‐resistant Staphylococcus aureus. The stereocontrolled installation of the olefinic double bonds at C2–C3/C3–C4 and C12–C13, respectively, as well as the orthogonal differentiation of the oxy functionalities turned out to be key challenges of our approach.

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Disciformycins A and B: 12‐Membered Macrolide Glycoside Antibiotics from the Myxobacterium Pyxidicoccus fallax Active against Multiresistant Staphylococci

Cited by 50 publications

References 32 publications

Myxochelins Target Human 5-Lipoxygenase

Myxochelins Target Human 5-Lipoxygenase

Myxobacteria in high moor and fen: An astonishing diversity in a neglected extreme habitat

Synthesis of the Aglycon of the Antibiotic Disciformycin

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