Covello Patrick S, Teoh Keat H, Polichuk Devin R, Reed Darwin W, Nowak Goska
Plant Biotechnology Institute, 110 Gymnasium Place, Saskatoon, SK, Canada S7N OW9.
Phytochemistry. 2007 Jul;68(14):1864-71. doi: 10.1016/j.phytochem.2007.02.016. Epub 2007 Mar 30.
Artemisinin, a sesquiterpene lactone endoperoxide derived from the glandular secretory trichomes (GSTs) of Artemisia annua, provides the basis for the most effective treatments of malaria. The biology and biochemistry of GSTs of the Asteraceae and their biosynthesis of isoprenoids is reviewed. Recent efforts to understand the biosynthesis of artemisinin in A. annua GSTs are discussed in detail. This includes the development in the authors' laboratory of an expressed sequence tag (EST) approach to identifying the relevant biosynthetic genes using isolated GST as a source of mRNA. This has lead to the isolation of a cDNA encoding CYP71AV1, a multifunctional cytochrome P450 which catalyzes multiple oxidations of the sesquiterpene intermediate amorpha-4,11-diene to artemisinic acid. Further biochemical and molecular genetic work is required to elucidate the precise route from artemisinic alcohol to artemisinin and to engineer more efficient low cost production of artemisinin-based antimalarial drugs.
青蒿素是一种从黄花蒿腺毛分泌的倍半萜内酯过氧化物，为疟疾最有效的治疗方法提供了基础。本文综述了菊科腺毛的生物学、生物化学及其类异戊二烯的生物合成。详细讨论了近期在理解黄花蒿腺毛中青蒿素生物合成方面所做的努力。这包括作者实验室开发的一种表达序列标签（EST）方法，该方法利用分离的腺毛作为mRNA来源来鉴定相关的生物合成基因。这已导致分离出一个编码CYP71AV1的cDNA，CYP71AV1是一种多功能细胞色素P450，它催化倍半萜中间体紫穗槐-4,11-二烯的多次氧化生成青蒿酸。需要进一步的生化和分子遗传学研究来阐明从青蒿醇到青蒿素的精确途径，并设计出更高效、低成本的基于青蒿素的抗疟药物生产方法。
