Phosphate control of pabS gene transcription during candicidin biosynthesis

The pabS gene of Streptomyces griseus IMRU3570 encodes the enzyme p-aminobenzoic acid synthase, which synthesizes p-aminobenzoic acid (PABA), a precursor of the antibiotic candicidin (Cd). The pabS transcript reached a peak at 12 h of incubation in batch cultures, preceding the formation of PABA synthase and the antibiotic itself. A decay of the pabS transcript was observed with an apparent half-life of 35 min. Inorganic phosphate (Pi; 7.5 mM) reduced the synthesis of the pabS transcript by 90-95%, and consequently the formation of PABA synthase and Cd. Thirty min after addition of 7.5 mM Pi, the cells synthesized only about 15% as much pabS transcript compared to control cultures. However, Pi stimulated two- to threefold total RNA synthesis. The 1.7-kb pabS transcript shown by Northern hybridization was greatly reduced in amount in cells grown in 7.5 mM phosphate. Pi-deregulated mutants, described previously, were impaired in the transcriptional control exerted by Pi. It is concluded that Pi control of PABA synthase and Cd biosynthesis is exerted by repression of formation of the pabS mRNA.