title: cis-fumagillin, a new methionine aminopeptidase (type 2) inhibitor produced by Penicillium sp. F2757.
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 (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 microg 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 microM). Compound 2 also inhibited the MetAP2 with an IC50 value of 9.2 nM and 105 microM against MetAP1.
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon, Republic of Korea.
authors.forename: J Y
authors.initials: JY
authors.lastname: Kwon
authors.forename: H W
authors.initials: HW
authors.lastname: Jeong
authors.forename: H K
authors.initials: HK
authors.lastname: Kim
authors.forename: K H
authors.initials: KH
authors.lastname: Kang
authors.forename: Y H
authors.initials: YH
authors.lastname: Chang
authors.forename: K S
authors.initials: KS
authors.lastname: Bae
authors.forename: J D
authors.initials: JD
authors.lastname: Choi
authors.forename: U C
authors.initials: UC
authors.lastname: Lee
authors.forename: K H
authors.initials: KH
authors.lastname: Son
authors.forename: B M
authors.initials: BM
authors.lastname: Kwon
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D004852:Epoxy Compounds / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D005285:Fermentation; D020128:Inhibitory Concentration 50; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D010407:Penicillium / Q000145:classification / Q000378:metabolism*
chemical_list: D004852:Epoxy Compounds; D005231:Fatty Acids, Unsaturated; C416816:fumagillin methyl ester; D000626:Aminopeptidases; C106541:methionine aminopeptidase 2; D008666:Metalloendopeptidases