Abstract
Selective inhibition against the yeast MetAP2 (methionine aminopeptidase type 2) was detected in the fermentation broth of a fungus F2757 that was later identified as Penicillium janczewskii. A new compound cis-fumagillin methyl ester (1) was isolated from the diazomethane treated fermentation extracts together with the known compound fumagillin methyl ester (2). The cis-fumagillin methyl ester, a stereoisomer of fumagillin methyl ester at the C2'-C3' position of the aliphatic side chain, selectively inhibited growth of the map1 mutant yeast strain (MetAPI deletion strain) at a concentration as low as 1 ng. However, the wild type yeast w303 and the mutant map2 (MetAP2 deleted) strains were resistant up to 10 μg of the compound. In enzyme experiments, compound 1 inhibited the MetAP2 with an IC50 value of 6.3nM, but it did not inhibit the MetAPl (IC50 >200μ, M). Compound 2 also inhibited the MetAP2 with an IC50 value of 9.2nM and 105 μM against MetAPl.
