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 stron gly inhibited by phosphate. p-Aminobenzoic acid (PABA) synthase activi ty, required for the synthesis of PABA, a candicidin precursor, was re duced by 72% in cells grown in medium supplemented with 7.5 mM phospha te. Hybridization studies showed that the DNA region of S. acrimycini carrying the pabAB gene (encoding PABA synthase) is very similar to th e homologous region of S. griseus 3570. S. acrimycini was easily trans formed with plasmids containing the pabAB gene of S. griseus. Four tra nsformants were studied in detail; three of the transformants synthesi zed 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 PAB A synthase and candicidin production was equally sensitive to phosphat e regulation in transformants with the pabAB than in the untransformed S. acrimycini strain.