cis-fumagillin, a new methionine aminopeptidase (type 2) inhibitor produced by Penicillium sp. F2757.
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.
Kwon
J Y
JY
Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon, Republic of Korea.
Jeong
H W
HW
Kim
H K
HK
Kang
K H
KH
Chang
Y H
YH
Bae
K S
KS
Choi
J D
JD
Lee
U C
UC
Son
K H
KH
Kwon
B M
BM
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*
D004852:Epoxy Compounds; D005231:Fatty Acids, Unsaturated; C416816:fumagillin methyl ester; D000626:Aminopeptidases; C106541:methionine aminopeptidase 2; D008666:Metalloendopeptidases