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黄花蒿(菊科)毛状体特异性cDNA揭示了CYP71AV1,一种在抗疟倍半萜内酯青蒿素生物合成中起关键作用的细胞色素P450。

Artemisia annua L. (Asteraceae) trichome-specific cDNAs reveal CYP71AV1, a cytochrome P450 with a key role in the biosynthesis of the antimalarial sesquiterpene lactone artemisinin.

作者信息

Teoh Keat H, Polichuk Devin R, Reed Darwin W, Nowak Goska, Covello Patrick S

机构信息

Plant Biotechnology Institute, 110 Gymnasium Place, Saskatoon, Sask., Canada S7N OW9.

出版信息

FEBS Lett. 2006 Feb 20;580(5):1411-6. doi: 10.1016/j.febslet.2006.01.065. Epub 2006 Jan 30.

Abstract

Artemisinin, a sesquiterpene lactone endoperoxide derived from the plant Artemisia annua, forms the basis of the most important treatments of malaria in use today. In an effort to elucidate the biosynthesis of artemisinin, an expressed sequence tag approach to identifying the relevant biosynthetic genes was undertaken using isolated glandular trichomes as a source of mRNA. A cDNA clone encoding a cytochrome P450 designated CYP71AV1 was characterized by expression in Saccharomyces cerevisiae and shown to catalyze the oxidation of the proposed biosynthetic intermediates amorpha-4,11-diene, artemisinic alcohol and artemisinic aldehyde. The identification of the CYP71AV1 gene should allow for the engineering of semi-synthetic production of artemisinin in appropriate plant or microbial hosts.

摘要

青蒿素是一种从植物黄花蒿中提取的倍半萜内酯过氧化物,是当今治疗疟疾最重要方法的基础。为了阐明青蒿素的生物合成过程,研究人员采用表达序列标签法,以分离出的腺毛作为信使核糖核酸(mRNA)来源,来鉴定相关的生物合成基因。一个编码细胞色素P450的cDNA克隆(命名为CYP71AV1)通过在酿酒酵母中的表达进行了表征,并被证明能催化假定的生物合成中间体 amorpha-4,11-diene、青蒿醇和青蒿醛的氧化反应。CYP71AV1基因的鉴定应该能够实现青蒿素在合适的植物或微生物宿主中的半合成生产工程。

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