青蒿素的合成生物学研究进展

  本文关键词：青蒿素的合成生物学研究进展，由笔耕文化传播整理发布。

青蒿素的合成生物学研究进展

药学学报 Acta Pharmaceutica Sinica 2013, 48 (2): 193?205 ? 193 ?

青蒿素的合成生物学研究进展

孔建强*, 王 伟, 程克棣, 朱 平

(中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室,

卫生部天然药物生物合成重点实验室, 北京 100050)

摘要: 青蒿素是应用广泛的一线抗疟药。现在市售的青蒿素主要是从植物中提取出来的, 含量稀少和需求广

泛导致青蒿素供应不稳定。建立一种环境友好、廉价的生产青蒿素的方法将是未来解决青蒿素来源问题的有效

方法。通过合成生物学技术来制备青蒿素, 利用细胞工厂将是未来青蒿素生产的主要方式。本综述简单介绍了

青蒿素的生物合成途径, 并对青蒿素生物合成相关基因, 如紫穗槐-4, 11-二烯氧化酶基因、细胞色素P450氧化还

原酶基因、青蒿醛双键还原酶和醛脱氢酶基因进行了重点介绍。此外, 本综述针对近年来青蒿素合成生物学发

展的特点以及影响底盘细胞制备目的产物的因素进行了详细的论述。

关键词: 青蒿素; 天然药物合成生物学; 底盘细胞; 模块; 元件

中图分类号: R931 文献标识码: A 文章编号: 0513-4870 (2013) 02-0193-13

Research progresses in synthetic biology of artemisinin

KONG Jian-qiang*, WANG Wei, CHENG Ke-di, ZHU Ping

(State Key Laboratory of Bioactive Substance and Function of Natural Medicines & Key Laboratory of Biosynthesis of

Natural Products, Ministry of Health of PRC, Institute of Materia Medica, Chinese Academy of Medical Sciences &

Peking Union Medical College, Beijing 100050, China)

Abstract: The first-line drug artemisinin is widely used against malaria. Commercially available artemisinin

is extracted from plants. However, the lack of sufficient raw material, artemisinin and the cost associated with the drug’s manufacture have limited the supply of ACT to most malaria sufferers in the Developing World.

As such, it is important to develop a low cost, fine to environment and high-quality method to supply sufficient

and reliable quantities of artemisinin in the future. The field of synthetic biology, which utilizes cell factories to manipulate microbial metabolism to enhance the production of artemisinin and its intermediates, has a particularly strong impact by providing new platforms for chemical production. After a brief introduction of the

artemisinin biosynthetic pathway, the present review focuses on the introduction of artemisinin biosynthetic genes,

such as the genes encoding amorpha-4, 11-diene monooxygenase, NADPH: cytochrome P450 oxidoreductase,

artemisinic aldehyde ?11(13) reductase and aldehyde dehydrogenase. The review also addresses general considerations for potential contributions of synthetic biology to artemisinin production, with an emphasis on

factors influencing interest compounds production in chassis cells.

Key words: artemisinin; synthetic biology of natural products; chassis cell; module; parts

?青蒿素是一种非常优良的抗疟药物, 存在活性好、毒副作用小、市场需求大、来源窄等特点, 从而 导致价格昂贵 , 不利于疾病的治疗和预防, 严重影响收稿日期: 2012-11-20; 修回日期: 2012-12-15. 人类的健康安全。因此, 需要建立一种大规模的、廉基金项目: 国家自然科学基金资助项目 (30701061).

*通讯作者 Tel: 86-10-63165169, Fax: 86-10-63165197,

E-mail: jianqiangk@imm.ac.cn 价生产这种药物的替代方法。现在看来, 天然药物合成生物技术无疑是最理想的。

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  本文关键词：青蒿素的合成生物学研究进展，，由笔耕文化传播整理发布。