Microbial hydroxylation of rustmicin (galbonolide A) and galbonolide B, two antifungal products produced by Micromonospora sp.

Ln order to synthesize derivatives of galbonolide A and B with improved che mical stability and antifungal activity profiles, a panel of microorganisms consisting of various species of actinomycetes and fungi were screened. As a result, an organism, Streptomyces halstedii, was identified, which catal yzed the formation of two polar compounds, one from each of the galbonolide s. The synthesis and the relative stability of these compounds were optimiz ed by using washed cells, which had been prepared from the transforming org anism, and reaction conditions, which included the usage of MES buffer with pH adjusted to 5.5 and incubation at 27 degreesC. Under conditions thus es tablished, two compounds were isolated and characterized by a combination o f UV, mass, and NMR spectroscopic analysis. The data indicate the synthesis of 21-hydroxy derivatives of galbonolides A and B with reduced but still s ignificant anti-fungal activity when compared to the parent galbonolides. ( C) 2001 Elsevier Science B.V. All rights reserved.