Melithiazols, New .BETA.-Methoxyacrylate Inhibitors of the Respiratory Chain Isolated from Myxobacteria. Production, Isolation, Physico-chemical and Biological Properties.

Abstract

Newantibiotic compounds, melithiazols, were isolated from the culture broth of strains of the myxobacteria Melittangium lichenicola, Archangium gephyra, and Myxococcus stipitatus. The compounds belong to the group of /?-methoxyaerylate (MOA)inhibitors and are related to the myxothiazols. The melithiazols show high antifungal activity, but are less toxic than myxothiazol A and its methyl ester in a growth inhibition assay with mouse cell cultures. The melithiazols inhibit NADHoxidation by submitochondrial particles from beef heart. Melithiazol A blocks the electron transport within the^-segment (complex III) and causes a red shift in the reduced spectrum of cytochrome b.During our screening for antibiotics from myxobacteria, wefound antifungal activities in the culture broth of two strains of Melittangium lichenicola, Me à¬26and Me à¬46.The activities were due to new compounds, which we named melithiazols0. Later, we also found these compounds in a strain ofArchangium gephyra, Ar 7747, and of Myxococcus stipitatus, Mxs64. In this paper we describe the production, isolation, and the physico-chemical and bio-

Antifungal antibiotics

“…Also, UK2A and UK3A do not have antibacterial activity or significant toxicity (Ueki et al 1997). A series of respiratory inhibitors (nearly 20 compounds) have been found from myxobacteria (Sasse et al 1999). Haliangicin isolated from a culture broth of the marine myxobacterium, Haliangium luteum, is a member of this class of compounds with a β-methoxyacrylate moiety which specifically inhibits the electron transport within the complex III of respiratory chain, like other β-methoxyacrylate inhibitors, such as myxothiazols, melithiazols and cystothiazoles (Fudou et al 2001a, b).…”

Complete Genome Sequence of Myxococcus stipitatus Strain DSM 14675, a Fruiting Myxobacterium

“…Myxobacteria are also rich sources of secondary metabolites, several of which have antibiotic or cytotoxic activities (4, 5). Among secondary metabolites produced by M. stipitatus , melithiazols have been shown to have antibiotic activity (6) and rhizopodin has been shown to have cytotoxic activity (7). However, the gene clusters encoding the enzymes involved in their biosynthesis have not been identified.…”

Pharmacologically Active Sulfur-Containing Compounds

“…New antibiotic compounds, melithiazoles (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) [18], were isolated from the culture broth of strains of the myxobacteria Melittangium lichenicolum, Archangium gephyra, and Myxococcus stipitatus. These compounds belong to the group of β-methoxyacrylate inhibitors and are related to the myxothiazoles.…”