BIOSYNTHESIS AND PHOSPHATE CONTROL OF CANDICIDIN BY STREPTOMYCES-ACRIMYCINI JI2236 - EFFECT OF AMPLIFICATION OF THE PABAB GENE

Biosynthesis of candicidin by Streptomyces acrimycini JI2236 was strongly inhibited by phosphate. p-Aminobenzoic acid (PABA) synthase activity, required for the synthesis of PABA, a candicidin precursor, was reduced by 72% in cells grown in medium supplemented with 7.5 mM phosphate. Hybridization studies showed that the DNA region of S. acrimycini carrying the pabAB gene (encoding PABA synthase) is very similar to the homologous region of S. griseus 3570. S. acrimycini was easily transformed with plasmids containing the pabAB gene of S. 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 the pabAB than in the untransformed S. acrimycini strain.