Regulation of Secondary Metabolite Biosynthesis: Catabolite Repression of Phenoxazinone Synthase and Actinomycin Formation by Glucose

Abstract

Synthesis of the secondary metabolite, actinomycin, and the enzyme, phenoxazinone synthase, involved in the biosynthesis of the antibiotic, were shown to be under severe catabolite repression by glucose. Of a variety of hexoses and carbon compounds examined, glucose, and to a lesser extent, mannose, proved to be the most repressive for enzyme synthesis. The repression by glucose was most evident before production of the antibiotic. In a chemically defined medium suitable for actinomycin production, synthesis of phenoxazinone synthase began at the time the glucose (0.1%) supply was depleted. Soon after, antibiotic synthesis was initiated. Galactose, the major carbon source for growth and antibiotic synthesis, was not utilized until the glucose was consumed. Generally, carbon compounds which supported a rapid rate of growth were most effective in producing catabolite repression.

Comparison of actinomycin peptide synthetase formation in Streptomyces chrysomallus and Streptomyces antibioticus

“…Actinomycin synthesis in S. antibioticus has been reported to be triggered through exhaustion of glucose during cultivation and that it was repressible by addition of glucose . Thus, to compare actinomycin formation (and peptide synthetase formation) in cultures of S. chrysomallus and S. antibioticus both strains were grown in a chemically defined medium containing glucose.…”

“…Previous work indicated that actinomycin synthesis in S. antibioticus was repressible by glucose, and that the onset of its formation in glucose‐containing cultures was with glucose exhaustion in the later stages of cultivation . Moreover, other work indicated that formation of AcmA in S. antibioticus was repressible by glucose, too.…”

“…The regulation of actinomycin biosynthesis has been previously investigated in actinomycin‐producing Streptomyces antibioticus and Streptomyces parvulus , which indicated that actinomycin production is subject to regulation by carbon and nitrogen sources. Several enzymes with a proposed role in actinomycin synthesis were shown to be repressible in their expression by glucose such as phenoxazinone synthase and actinomycin synthetase I (AcmA) from S. antibioticus . Other studies concerning regulation of actinomycin synthesis addressed the role of the gene sigE encoding, a sigma factor of the ECF family of sigma factors in S. antibioticus .…”

Sequential Optimization Approach for Enhanced Production of Antimicrobial Compound from <I>Streptomyces rochei</I> BKM-4

“…RUPA-08PR which was found to produce high levels of antimicrobial metabolites in the medium supplemented with glucose (2%) as sole carbon source (Ripa et al, 2009). Higher glucose concentration has been reported to repress the formation of phenoxazinone synthetase, an enzyme required for producing antibiotic compound namely actinomycin synthesis (Gallo and Katz 1972) and higher glucose concentration will effect to metabolite repression, and production of secondary metabolite will decrease significant (Sunaryanto 2012).…”

Screening of Antagonistic Marine Actinomycetes: Optimization of Process Parameters for the Production of Novel Antibiotic by Amycolatopsis Alba var. nov. DVR D4

“…Similar observation was reported by Syed et al [39] that 2.0 %w/v D-glucose was found to be the optimum concentration for maximum antibiotic production. High concentration of glucose is generally considered as repressor of secondary metabolisms [40] and maximum cell growth rates can inhibit antimicrobial agent production [41]. A catabolic repression of secondary metabolism produced by actinomycetes during actinomycin synthesis by Streptomyces antibioticus was reported after the addition of more glucose in the medium [42].…”