Promomycin, a polyether promoting antibiotic production in Streptomyces spp.

Abstract

Widespread interspecific stimulation of antibiotic production occurs in strains of Streptomyces owing to the activity of diffusible substances, as previously determined in our investigations of the cross-feeding effect. In this study, we newly isolated a substance produced by a Streptomyces strain closely related to Streptomyces scabrisporus, based on the observation that this substance induced the production of an unknown antibiotic in another strain related to Streptomyces griseorubiginosus. This substance, named promomycin, is a polyether structurally related to lonomycin. Promomycin itself had an antibiotic activity, but it stimulated antibiotic production in multiple Streptomyces strains at sub-inhibitory concentrations. Evidence implies that this stimulation effect is widespread within this group of bacteria. The Journal of Antibiotics (2010) Keywords: antibiotic production; ionophore; polyether; promomycin; Streptomyces INTRODUCTION Antibiotic production in Streptomyces is affected by various environmental stimuli. 1 Accumulating evidence has shown that specific diffusible metabolites in addition to physicochemical stimuli induce antibiotic production in Streptomyces. Such metabolites include gbutyrolactone autoregulators, which are the best-characterized hormonal signals in Streptomyces and are widely distributed among members of this genus. Since the discovery of A-factor (2-isocapryloyl 3R-hydroxymethy-g-butyrolactone), secondary metabolism in Streptomyces has been shown to be generally controlled by this type of signal produced by the organism itself. 2 Both structural diversity and ligandreceptor specificity indicate that g-butyrolactone sensing occurs in an intraspecific manner, rather than in an interspecific manner.In contrast to the concept of autoregulation, our previous observations have shown that interspecific stimulation of secondary metabolism and/or morphogenesis takes place among various Streptomyces species and other related bacteria. 3 Cross-feeding assays on solid media (see Figure 1a as a reference) have shown that an array of colonies of one strain (corresponding to strain 574 in Figure 1a) responded to a concentration gradient of a substance diffusing from the colony of another strain (corresponding to strain 153 in Figure 1a). To determine whether such stimulatory events between different species involve unknown specific metabolites, we have attempted to isolate the metabolites responsible for the stimulatory activity. We recently identified desferrioxamines, which represent a

Lincomycin at Subinhibitory Concentrations Potentiates Secondary Metabolite Production by Streptomyces spp

“…The protein synthesis inhibitors chloramphenicol and erythromycin alter the expression of genes involved in amino acid metabolism in B. subtilis 168 (49). In streptomycetes, the polyether antibiotics promomycin and monensin have been shown to induce antibiotic production by Streptomyces strains (50,51). Rifampin, an RNA polymerase inhibitor, and oligomycin A, a mitochondrial ATP synthase inhibitor, cause changes in antibiotic (ACT or RED) production and aerial hyphal development in S. coelicolor (17).…”

Antibiotic dialogues: induction of silent biosynthetic gene clusters by exogenous small molecules

“…1, 4). It was discovered as an elicitor in an interaction where one Streptomyces strain promoted production of an otherwise cryptic antibiotic in another (Amano et al 2010). The eliciting molecule, promomycin, was shown to be a polyether antibiotic, structurally similar to lonomycin.…”

Prospecting for new bacterial metabolites: a glossary of approaches for inducing, activating and upregulating the biosynthesis of bacterial cryptic or silent natural products

“…60 Other polyethers, salinomycin (35), monensin (36) and nigercin (37) had similar effects, inducing antibiotic production in isolated strains when administered at SIC. 60 Recently, one of the antibiotics whose production was induced by the administration of SICs of monensin to the producing strain, Streptomyces griseorubiginosus strain 574, was identified as the isonitrile antibiotic SF2768 (38). 61 Although not an antibiotic, the commercially available siderophore desferrioxamine E (39) produced by a number of Streptomyces spp., has been shown to induce and elevate the biosynthesis of some metabolites.…”