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Tubulysins are a group of secondary metabolites produced by myxobacteria that inhibit the function of the eukayotic cytoskeleton. We developed a pair of PCR primers that specifically amplified tubulysin biosynthetic genes. Using these primers, eight out of the eighty-one strains of myxobacteria belonging to the Cystobacteraceae family that harbored putative tubulysin biosynthetic genes were screened through PCR analysis. The selected strains included two Archangium gephyra, two Stigmatella sp., two Vitiosangium cumulatum, and two unidentified myxobacteria. LC-MS analysis of the culture extracts from the selected strains revealed that A. gephyra KYC4066 produced putative tubulysin A and B.

Natural products have long been a source of useful biological activity for the development of new drugs. Their macromolecular targets are, however, largely unknown, which hampers rational drug design and optimization. Here we present the development and experimental validation of a computational method for the discovery of such targets. The technique does not require three-dimensional target models and may be applied to structurally complex natural products. The algorithm dissects the natural products into fragments and infers potential pharmacological targets by comparing the fragments to synthetic reference drugs with known targets. We demonstrate that this approach results in confident predictions. In a prospective validation, we show that fragments of the potent antitumour agent archazolid A, a macrolide from the myxobacterium Archangium gephyra, contain relevant information regarding its polypharmacology. Biochemical and biophysical evaluation confirmed the predictions. The results obtained corroborate the practical applicability of the computational approach to natural product 'de-orphaning'.

[structure: see text] The relative and absolute stereochemistry of the structurally unique 24-membered myxobacterial macrolides archazolid A and B, highly potent vacuolar-type ATPase (V-ATPase) inhibitors in vitro and in vivo, was determined on the basis of a combination of extensive high-field NMR studies, including J-based configuration analysis, molecular modeling, and chemical methods.

The novel antifungal metabolites cyrmenin A, B1, and B2 (1−3) were isolated from Archangium gephyra and Cystobacter armeniaca strains (myxobacteria). The cyrmenins are modified N-acyldipeptide esters containing a didehydroalanine, a 3-O-methyl-didehydroserine and a (2E,4Z)-undecadienoic or -dodecadienoic acid residue. These compounds represent the first bacterial counterparts of strobilurins that are characterized by an α-substituted β-methoxyacrylate pharmacophore. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

The structure of the title compound, a constituent of the myxobacterium Archangium gephyra (Ar 3895) which exists as a separable mixture of keto and hemiketal isomers, is unambiguously confirmed as (I).

The ultrastructure of natural myxospores and glycerol-induced myxospores has been studied in four Archangium gephyra strains (AG3, AG5, AG9, and AG10). The induced myxospores show an oval shape, characteristic of the genus Archangium, and an electron-dense coat surrounds the cell wall. The cytoplasm contains abundant electron-lucent inclusions. Sometimes, a membranous structure appears between the coat and the outer membrane. The fruiting-body myxospores show an oval shape similar to that observed in induced myxospores, but with a slightly thicker outer coat. In many of the natural myxospores, some membranous, lamellar or vesicular structures appear. They are located between the coat and the outer membrane, resembling those that appeared in induced myxospores. These have not been previously mentioned in papers on fruiting-body myxospores. These structures occasionally seem to be fused, giving rise to membranous sacs filled with an amorphous material of medium electron density. We propose that these vesicles are formed from the waved outer membrane and from the fruiting-body matrix. Large, dense, fusiform inclusions with an internal crystalline array are frequently found in the cytoplasm of natural myxospores, and cells during differentiation, in strains AG3, AG9, and AG10. Key words: Archangium gephyra, electron microscopy, myxospores, ultrastructure.

Summary A reduction in the cellular levels of the cyclin kinase inhibitor p27 kip1 is frequently found in many human cancers and correlates directly with patient prognosis. In this work, we identify argyrin A, a cyclical peptide derived from the myxobacterium Archangium gephyra , as a potent antitumoral drug. All antitumoral activities of argyrin A depend on the prevention of p27 kip1 destruction, as loss of p27 kip1 expression confers resistance to this compound. We find that argyrin A exerts its effects through a potent inhibition of the proteasome. By comparing the cellular responses exerted by argyrin A with siRNA-mediated knockdown of proteasomal subunits, we find that the biological effects of proteasome inhibition per se depend on the expression of p27 kip1 .

The archazolids are complex polyketides isolated from the myxobacterium Archangium gephyra and are potent inhibitors of vacuolar type ATPases. Herein, we report the first total synthesis of archazolid A, which establishes unequivocally the relative and absolute configuration of this macrolide antibiotic. Key features of our synthesis include an aldol condensation for construction of the delicate (Z,Z,E)-triene-system, an E-selective Heck reaction on a highly elaborate substrate, and a HWE macrocyclization to close the 24-membered macrolactone.

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.

Novel cytotoxic compounds, archazolid A and B, were isolated from the culture broth of strains of the myxobacteria Archangium gephyra and Cystobacter sp. Archazolids consist of a macrocyclic lactone ring with a thiazole side chain and showed high activity against mammalian cells. The IC50 values with different cell lines ranged from 0.1 to 1 ng/ml. An incubation of PtK2 potoroo cells with archazolid A (5 ng/ml) led to the formation of vacuoles in the ER, a phenomenon that is typical for inhibitors of V-ATPases, like concanamycin and bafilomycin. We therefore assume that archazolid is an inhibitor of the V-ATPase of higher cells.

140 leaf samples were examined, 73 of which ( = 52.1%) contained myxobacteria. Three species of the genus Myxococcus, M. virescens, M. fulvus and M. coralloides, could be found more or less frequently in the phyllosphere of woody plants and annuals. Archangium gephyra was observed only once. There was no significant difference in the occurrence of myxobacteria between evergreen leaves and leaves from deciduous trees and shrubs. Fruit-trees yielded the best results.

Myxobacterial species, Archangium gephyra and Archangium primigenium, were isolated from elm tree bark and soil in central Missouri. Pure cultures of these isolates were obtained by quick transfer ...