MICROBIAL MODIFICATION OF PRADIMICINS AT C-11 LEADING TO 11-O-DEMETHYLPRADIMICINS AND 11-0-L-XYLOSYLPRADIMICINS A AND FA-1

In a screen of pradimicin-nonproducing mutants derived from Actinomadura verrucosospora subsp. neohibisca R103-3, we found a strain capable of producing 11-hydroxyl analogs of pradimicins A and FA-1, designated pradimicins H and FH, respectively. Feeding of pradimicins H and FH to growing cultures of an actinomycete strain AA3798 produced 11-O-L-xylosylpradimicins H and FH, respectively. These 11-O-L-xylosylpradimicins had a broad spectrum of antifungal activity and demonstrated in vivo efficacies against Candida albicans in mice.