BIOSYNTHESIS OF GANEFROMYCIN - RESULTS FROM BLOCKED MUTANTS AND BIOCONVERSION EXPERIMENTS

The biosynthetic pathway of ganefromycin alpha (8) was investigated us ing blocked mutants of Streptomyces lydicus spp. tanzanius, the ganefr omycin alpha producer, in conjunction with bioconversion experiments w ith the products of these mutants. Compounds 1-7 and 9-15, which are s tructurally related to ganefromycin alpha, were produced by cultures o f secretor mutants showing blockage or diminished production of 8. The se compounds were isolated, characterized, and subjected to bioconvers ion experiments using converter and other secretor mutants. Some of th e compounds were shown to be products resulting from blocks at various stages in the biosynthetic pathway beyond construction of the polyket ide skeleton (e.g., furan ring closure, hydroxylation, glycosylation, etc.). Other compounds were not bioconverted by biosynthetically capab le mutants and were deemed shunt products. A mutant's metabolites and bioconverting ability were used to surmise the location of the block. A picture of the later sequence of events leading to the synthesis of ganefromycin alpha emerged, including C23-hydroxylation, C13a-O-methyl ation, C21a-hydroxylation, and C21a-O-glycosylation. Some of the later steps in the biosynthetic pathway for ganefromycin alpha are proposed .