Bacterial degradation of microcystins and nodularin

被引:114
作者
Imanishi, S
Kato, H
Mizuno, M
Tsuji, K
Harada, K
机构
[1] Meijo Univ, Grad Sch Environm & Human Sci, Tempa Ku, Nagoya, Aichi 4688503, Japan
[2] Meijo Univ, Fac Pharm, Tempa Ku, Nagoya, Aichi 4688503, Japan
[3] Kanagawa Prefectural Inst Publ Hlth, Kanagawa 2530087, Japan
关键词
D O I
10.1021/tx049677g
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Microcystins and nodularins produced by cyanobacteria are potent hepatotoxins and tumor promoters. They are, respectively, cyclic heptapeptides and cyclic pentapeptides containing a characteristic beta-amino acid residue, (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4(E),6(E)-dienoic acid (Adda). Strain B-9 isolated from Lake Tsukui, Japan, degrades microcystin-LR, which is the most toxic among the microcystins, to nontoxic Adda as an end product. In the present study, we characterized the bacterial degradation process of the cyclic peptide hepatotoxins by liquid chromatography/ion trap tandem mass spectrometry. The use of protease inhibitors with a B-9 cell extract indicated that the degradation process of microcystin-LR consists of sequential enzymatic hydrolyses of Arg-Adda, Ala-Leu, and then Adda-Glu peptide bonds into two known nontoxic intermediate degradation products and then Adda, respectively. Subsequently, additional microcystins and nodularin were compared with microcystin-LR on substrate specificity. The cyclic peptides containing the Arg-Adda peptide bond were almost completely degraded to Adda as well as microcystin-LR, whereas microcystin-LF containing the Phe-Adda peptide bond instead of Arg-Adda peptide bond and 6(Z)-Adda-microcystin-LR and -RR which are geometrical isomers of the Adda residue were barely degraded. These results indicated that the degrading enzymes selectively hydrolyzed the Arg-Adda peptide bond as the initial ring opening of the cyclic peptide hepatotoxins, microcystins and nodularin.
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页码:591 / 598
页数:8
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