Pigmented antibiotic production by Streptomyces coelicolor A3(2): kinetics and the influence of nutrients

Abstract

~_ _ _ _ _ _~ _ _ _ _ _ _ _~The production of the pigments actinorhodin and undecylprodigiosin by Stveptomyces coelicolor A3(2) was examined in a chemically defined medium which permits dispersed growth of the organism. The physiological controls on the production of the two pigments were markedly disparate. Actinorhodin production occurred mainly in the stationary phase of batch cultures grown with glucose and sodium nitrate as the principal carbon and nitrogen sources. In the same batch cultures, undecylprodigiosin accumulated during the exponential growth phase. The production of both pigments was sensitive to the levels of ammonium and phosphate in the medium. Actinorhodin production was exquisitely sensitive to ammonium concentration, and was completely inhibited by as little as 1 mM-ammonium chloride, whereas more than 50 mhl-amnonium chloride was required to prevent undecylprodigiosin production. A similar, but less extreme effect was seen with phosphate: actinorhodin production was completely inhibited by 24 mM-phosphate, whereas undecylprodigiosin was still formed at this high phosphate concentration. The effects of ammonium inhibition of pigmented antibiotic production were relieved by reducing the concentration of phosphate in the medium, but changing the ammonium concentration had no effect on phosphate inhibition. Thus the regulation of pigment production by these two nutrients is interrelated, with phosphate control being epistatic to that of ammonium. The results implicate a phosphorylated intermediate as a major regulator of secondary metabolite synthesis by S. coelicolor.

An integrated approach to studying regulation of production of the antibiotic methylenomycin by Streptomyces coelicolor A3(2)

“…Effect of nitrogen source on methylenomycin production. Our previous studies on antibiotic production by S. coelicolor A3(2) strain 1147 employed a minimal medium containing an inorganic nitrogen source (12). In none of these experiments was any production of methylenomycin detected, whereas the presence of actinorhodin could be demonstrated.…”

“…Phosphate concentration is known to greatly influence antibiotic synthesis in streptomycetes (23,24,29). We had previously found that the production of actinorhodin by S. coelicolor grown on minimal medium containing an inorganic nitrogen source was subject to phosphate regulation (12). Moreover, regulation by phosphate was found to be epistatic to that exerted by the nitrogen source, since it was possible to relieve the ammonium inhibition of the actinorhodin production by lowering the phosphate concentration from 11 to 1 mM.…”

“…An alternative approach to achieving such metabolic channeling is the use of physiological steering, in which growth conditions are adjusted so as to inhibit or repress certain pathways and favor others. The laboratory model organism S. coelicolor A3(2) synthesizes at least four secondary metabolites (see above), and we have already used physiological steering to dissociate the synthesis of the two pigmented products, actinorhodin and undecylprodigiosin (12).…”

“…This organism produces a range of secondary metabolites, including actinorhodin, undecylprodigiosin, calciumdependent antibiotic, and methylenomycin A. The recent development of a defined medium that permits the dispersed growth of S. coelicolor in either batch or continuous culture (11) has allowed the physiological controls that operate on the synthesis of the first two of these products to be elucidated (12).…”

Characterization and fluorescence of yellow biofilms in karst caves, southwest Slovenia

“…Roles in other ecological interactions should also be considered, e.g. protection against grazers by production of antibiotics, as with Streptomyces (Hobbs et al, 1990), or secretion of siderophores. Siderophores are important in virulence (pathogenicity) expression and development of biofilms by different microbes (Wynn-Williams et al, 2002;Saha et al, 2013).…”