青蒿素及其衍生物的生物合成

The biosynthesis of artemisinin and its derivatives

青蒿素(artemisinin,ART)是一种含有独特过氧桥结构的倍半萜内酯类化合物,是目前治疗恶性疟疾的首选药物。近年来研究发现,青蒿素及其衍生物还具有其他多种药理作用。黄花蒿中青蒿素含量为0.01%~0.80%,且传统提取工艺得率很低,成本较高。随着合成生物学技术的不断发展,越来越多的科研人员致力于青蒿素的生物合成途径的解析以及代谢工程的研究,以提高青蒿素的产量。然而,由于青蒿素终端生物合成途径尚未被解析,目前青蒿素仍主要来源于植物提取,与传统的生产方法相比,以生物反应器大规模生产青蒿素被视为一个重要的替代方法。本文从青蒿素的生物合成途径、异源合成、转录因子及其代谢调控等多个方面进行综述,旨在为绿色、高效生产青蒿素提供科学资料。

Artemisinin,a sesquiterpene lactone with a special endoperoxide bond,is the first choice for treating falciparum malaria.It also has other significant pharmacologically effections.However,Artemisia annua has very low artemisinin content(0.01%~0.80%),and the products that are created using the old extraction method are expensive and have low content,making it difficult to meet market demand.A growing number of scientists have dedicated to study the biosynthesis pathway of artemisinin and metabolic engineering to enhance artemisinin production in recent years,along with the ongoing advancement of synthetic biology.Since the artemisinin’s terminal biosynthesis pathway has not yet been finished,clarifried compound is still primarily isolated from plants.This paper reviews the biosynthetic pathways,heterologous synthesis,transcription factors,and metabolic regulation of artemisinin.It also offers a proposed scientific information for the efficient and environmentally friendly production of artemisinin,suggesting that largescale bioreactor production of the drug could be a significant alternative to conventional methods.