Actinorhodin and undecylprodigiosin production in wild-type and relA mutant strains of Streptomyces coelicolor A3(2) grown in continuous culture

Abstract

The effects of growth rate and nutrient feed rate on the productionof actinorhodin (Act) and undecylprodigiosin (Red) were determinedin Streptomyces coelicolor A3(2) and in a congenic relA null-mutantknown to be deficient in ppGpp synthesis and antibiotic productionunder conditions of nitrogen limitation. In the relA+ strain, Actproduction was inversely related to specific growth rate in continuouscultures limited by glucose, ammonium, or phosphate, while Red biosynthesiswas optimal at 0.05 h-1 regardless of the specific nutrient limitation.Production of Act and Red in the relA mutant was lower than thatof the parental strain, particularly under conditions of glucose-and ammonium-limitation, indicating an important and general rolefor ppGpp in determining the onset of the antibiotic biosynthesisunder conditions of nutrient limitation. At constant growth rate,but with varying nutrient feed rates, the specific rate of Act productionwas adversely influenced by increasing levels of glucose, ammonium,and phosphate, with phosphate having the greatest inhibitory effect.Under the same conditions, the specific rate of Red production wasstimulated by increasing glucose levels, but markedly decreased byincreased levels of phosphate.