Isolation, structure determination and biological activity of 15-deoxo-7,32-O-didesmethylrapamycin from the soil actinomycete LL-D45042.

Rapamycin (1) is a potent immunosuppressive and antiproliferative natural product isolated from the soil actinomycete Streptomyces hygroscopicus NRRL 5491.1) The final steps in the biosynthesis of rapamycin involve oxidations at C15 and C32 by cytochromes P-450 and three methylations on oxygens at C7, C32, and C41.2) Many of the possible biosynthetic intermediates that lack full elaboration at these positions have been isolated and characterized.3) In the course of evaluating rapamycin producers in our collection of actinomycetes, we encountered a new strain, designated LL-D45042, that makes the previously unreported rapamycin intermediate, 15-deoxo-7,32-Odidesmethylrapamycin (2). We herein report the preliminary characterization of the strain, and the isolation, structure determination and biological activity of the new compound. Culture LL-D45042 sporulated moderately to abundantly on most media studied with aerial mycelium in the Greycolor series. The 16S rDNA sequence was determined for strain LL-D45042 following isolation and direct sequencing of the amplified gene and supported classification of the strain in the genus and species of S. hygroscopicus. Physiological studies4) of culture LL-D45042 resulted in no melanin production, slow starch hydrolysis, decomposition of and fair growth on cellulose, no hydrogen sulfide production, and good digestion of casein. Carbohydrate utilization tests indicated good growth on D-