Cis-fumagillin, a new methionine aminopeptidase(yp 2) inhibitor produced by Penicillium sp. F2757

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Title
Cis-fumagillin, a new methionine aminopeptidase(yp 2) inhibitor produced by Penicillium sp. F2757
Author(s)
Ju Young Kwon; Ha Won Jeong; Hyae Kyeong Kim; Kui Hyun Kang; Yie Hwa Chang; Kyung Sook Bae; Jung Do Choi; Un Chul Lee; Kwang Hee Son; Byoung-Mog Kwon
Bibliographic Citation
Journal of Antibiotics, vol. 53, no. 8, pp. 799-806
Publication Year
2000
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 map 1 mutant yeast strain (MetAP1 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 6.3 nM, but it did not inhibit the MetAP1 (IC50 >200 μM). Compound 2 also inhibited the MetAP2 with an IC50 value of 9.2 nM and 105 μM against MetAP1.
ISSN
0021-8820
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.7164/antibiotics.53.799
Type
Article
Appears in Collections:
Division of Biomedical Research > Microbiome Convergence Research Center > 1. Journal Articles
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