The myxovirescins, a family of antibiotics from Myxococcus virescens (Myxobacterales).

Abstract

The myxobacterium, Myxococcus virescens strain Mx v48 produced a family of at least 12 closely related antibiotics, the myxovirescins***.At a concentration of 1 to 5 iig/ml, the main component, myxovirescin A, was bactericidal for many Gram-negative bacteria, in particular enterobacteria, and at 20 to 50 Egg/ml it also inhibited some pseudomonads and Grampositive bacteria. The antibiotics seem to interfere with cell wall synthesis. The molecular formula of myxovirescin A was C35H61NO3. It is a new antibiotic. Batch cultures of 100 ml were incubated in 250-m1 Erlenmeyer flasks at 32°C on a rotary shaker at 160 cycles per minute. Under these conditions, Mx v48 grew as a cell suspension with a generation time of 5 to 6 hours. The antibiotic activity appeared in the culture supernatant. As the yield was very low (about 0.2 leg/ml), the antibiotic could be demonstrated by the paper disk method only after concentrating the broth 50: 1. No antibiotic could be extracted from the cells with acetone or methanol.The activity was excreted only during exponential growth and disappeared again before the culture entered the stationary phase. Growth of the producing organism was inhibited by its own antibiotic by 50% at a concentration of 0.25 µg/ml. We therefore isolated mutants that were resistant against the antibiotic. These, as all other mutants isolated in the course of this study, were obtained by treat ment with N-methyl-N'-nitro-N-nitrosoguanidine. One of the Mutants, Mx v48-M3, was resistant against 30 to 40 pg/ml of the antibiotic. It still produced only 0.2 fig/ml, but production was now at the end of the growth phase, and the antibiotic remained stable during the following stationary phase.We then looked for mutants with higher yields. Mutagenized cultures of Mx v48-M3 were plated, and after 10 days the developing colonies were covered with a thin layer of agar containing cells of Escherichia

Membrane Localization of Motility, Signaling, and Polyketide Synthetase Proteins in Myxococcus xanthus

“…It is possible that the myxovirescin A biosynthetic machinery is associated with phospholipid to protect the peptidoglycan. This hypothesis is consistent with experiments indicating that myxovirescin A activity is inhibited by phospholipids (11).…”

“…Myxovirescin A inhibits peptidoglycan synthesis in a wide range of gram-negative cells, including cells of the producing organism. M. virescens displays twofold-greater sensitivity to myxovirescin A than E. coli (11). In contrast, 60-fold more myxovirescin A was required to inhibit cell growth of P. aeruginosa.…”

“…Myxovirescin A is produced during exponential growth and has been purified from culture supernatants (11). The membrane association of PKS probably facilitates safe export of the final product.…”

Myxobacterial secondary metabolites: bioactivities and modes-of-action

“…The mixed polyketide-nonribosomal polypeptide myxovirescin 44 (antibiotic TA), [83][84][85] acts at an earlier stage, interfering with cell wall synthesis by inhibiting the incorporation of N-acetyl-glucosamine. 86 Myxovirescin exhibits a second useful property which is strong adherence to a variety of surfaces, including dental tissues and rubber, while retaining its antimicrobial activity.…”

Identification of Functions Affecting Predator-Prey Interactions between Myxococcus xanthus and Bacillus subtilis

“…For M. xanthus, the specialized metabolite myxovirescin (also known as TA) is necessary for predation of proteobacteria by inhibiting lipoprotein production (9,22,23). Other specialized metabolites found in membrane vesicles or secreted by M. xanthus comprise part of the predation machinery.…”