Ansamitocin analogs from a mutant strain of Nocardia. I. Isolation of the mutant, fermentation and antimicrobial properties.

A mutant having a high ability to produce ansamitocins was derived from a dnacin-producing strain, Nocardia sp. No. C-14482 (N-1001), by treatment with ethidium bromide. Mutant N-1231 produced ansamitocins P-3 and P-4 as major components, but was deficient in its ability to produce dnacins. Strain N-1231 also produced fifteen novel ansamitocin analogs as minor components. These analogs showed no activity against prokaryotic micro-organisms. The results of determining the activity inhibiting cilia regeneration of deciliated Tetrahymena pyriformis suggest that hydroxylation of C15, C26 and the acyl moiety at C3 of ansamitocins may cause marked reduction of their antitubulinic activities whereas demethylation of -NCH3 at C18 slightly affected their activities.