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

In order to synthesize derivatives of galbonolide A and B with improved chemical 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 catalyzed the formation of two polar compounds, one from each of the galbonolides. The synthesis and the relative stability of these compounds were optimized by using washed cells, which had been prepared from the transforming organism, and reaction conditions, which included the usage of MES buffer with pH adjusted to 5.5 and incubation at 27°C. Under conditions thus established, two compounds were isolated and characterized by a combination of UV, mass, and NMR spectroscopic analysis. The data indicate the synthesis of 21-hydroxy derivatives of galbonolides A and B with reduced but still significant anti-fungal activity when compared to the parent galbonolides.