DIRECTED BIOSYNTHESIS OF 5''-FLUOROPACTAMYCIN IN STREPTOMYCES-PACTUM

A new pactamycin analogue, 5''-fluoropactamycin, was prepared by directed biosynthesis. Supplementation of the fermentation medium of Streptomyces pactum, var. pactum with 3-amino-5-fluorobenzoic acid, an analogue of 3-aminobenzoic acid, an advanced precursor in pactamycin biosynthesis, resulted in co-production of pactamycin and the new pactamycin analogue. A similar feeding experiment with 3-amino-5-methylbenzoic acid did not result in formation of the corresponding methylated pactamycin analogue, but only in inhibition of pactamycin production. Comparison of antimicrobial and cytotoxic activities of pactamycin and 5''-fluoropactamycin showed no significant differences.