黑腹果蝇CYP6A8，一种催化月桂酸（ω-1）羟基化的昆虫细胞色素P450。

Drosophila melanogaster CYP6A8, an insect P450 that catalyzes lauric acid (omega-1)-hydroxylation.

作者信息

Helvig Christian, Tijet Nathalie, Feyereisen René, Walker F Ann, Restifo Linda L

机构信息

Department of Chemistry, The University of Arizona, Tucson, AZ 85721, USA.

出版信息

Biochem Biophys Res Commun. 2004 Dec 24;325(4):1495-502. doi: 10.1016/j.bbrc.2004.10.194.

DOI:10.1016/j.bbrc.2004.10.194

PMID:15555597

Abstract

Only a handful of P450 genes have been functionally characterized from the approximately 90 recently identified in the genome of Drosophila melanogaster. Cyp6a8 encodes a 506-amino acid protein with 53.6% amino acid identity with CYP6A2. CYP6A2 has been shown to catalyze the metabolism of several insecticides including aldrin and heptachlor. CYP6A8 is expressed at many developmental stages as well as in adult life. CYP6A8 was produced in Saccharomyces cerevisiae and enzymatically characterized after catalytic activity was reconstituted with D. melanogaster P450 reductase and NADPH. Although several saturated or non-saturated fatty acids were not metabolized by CYP6A8, lauric acid (C12:0), a short-chain unsaturated fatty acid, was oxidized by CYP6A8 to produce 11-hydroxylauric acid with an apparent V(max) of 25 nmol/min/nmol P450. This is the first report showing that a member of the CYP6 family catalyzes the hydroxylation of lauric acid. Our data open new prospects for the CYP6 P450 enzymes, which could be involved in important physiological functions through fatty acid metabolism.

摘要

在最近在黑腹果蝇基因组中鉴定出的约90个P450基因中，只有少数几个已得到功能表征。Cyp6a8编码一种506个氨基酸的蛋白质，与CYP6A2的氨基酸同一性为53.6%。CYP6A2已被证明可催化包括艾氏剂和七氯在内的几种杀虫剂的代谢。CYP6A8在许多发育阶段以及成年期均有表达。CYP6A8在酿酒酵母中产生，并在用黑腹果蝇P450还原酶和NADPH重建催化活性后进行酶学表征。尽管几种饱和或不饱和脂肪酸未被CYP6A8代谢，但短链不饱和脂肪酸月桂酸（C12:0）被CYP6A8氧化生成11-羟基月桂酸，表观V(max)为25 nmol/min/nmol P450。这是首次报道CYP6家族成员催化月桂酸的羟基化。我们的数据为CYP6 P450酶开辟了新的前景，其可能通过脂肪酸代谢参与重要的生理功能。