Biosynthesis and phosphate control of candicidin byStreptomyces acrimycini JI2236: effect of amplification of thepabAB gene

Summary Biosynthesis of candicidin byStreptomyces acrimycini JI2236 was strongly inhibited by phosphate.p-Aminobenzoic acid (PABA) synthase activity, required for the synthesis of PABA, a candicindin precursor, was reduced by 72% in cells grown in medium supplemented with 7.5 mM phosphate. Hybridization studies showed that the DNA region ofS. acrimycini carrying thepabAB gene (encoding PABA synthase) is very similar to the homologous region ofS. griseus 3570.S. acrimycini was easily transformed with plasmids containing thepabAB gene ofS. griseus. Four transformants were studied in detail; three of the transformants synthesized higher levels of PABA synthase and two transformants produced more candicidin than control cultures transformed with pIJ699. The fourth transformant was unable to synthesize the antibiotic. Formation of PABA synthase and candicidin production was equally sensitive to phosphate regulation in transformants with thepabAB than in the untransformedS. acrimycini strain.