本文關(guān)鍵詞：青蒿素的合成生物學(xué)研究進(jìn)展，由筆耕文化傳播整理發(fā)布。

青蒿素的合成生物學(xué)研究進(jìn)展

藥學(xué)學(xué)報(bào) Acta Pharmaceutica Sinica 2013, 48 (2): 193?205 ? 193 ?

青蒿素的合成生物學(xué)研究進(jìn)展

孔建強(qiáng)*, 王 偉, 程克棣, 朱 平

(中國(guó)醫(yī)學(xué)科學(xué)院、北京協(xié)和醫(yī)學(xué)院藥物研究所, 天然藥物活性物質(zhì)與功能國(guó)家重點(diǎn)實(shí)驗(yàn)室,

衛(wèi)生部天然藥物生物合成重點(diǎn)實(shí)驗(yàn)室, 北京 100050)

摘要: 青蒿素是應(yīng)用廣泛的一線抗瘧藥�，F(xiàn)在市售的青蒿素主要是從植物中提取出來(lái)的, 含量稀少和需求廣

泛導(dǎo)致青蒿素供應(yīng)不穩(wěn)定。建立一種環(huán)境友好、廉價(jià)的生產(chǎn)青蒿素的方法將是未來(lái)解決青蒿素來(lái)源問(wèn)題的有效

方法。通過(guò)合成生物學(xué)技術(shù)來(lái)制備青蒿素, 利用細(xì)胞工廠將是未來(lái)青蒿素生產(chǎn)的主要方式。本綜述簡(jiǎn)單介紹了

青蒿素的生物合成途徑, 并對(duì)青蒿素生物合成相關(guān)基因, 如紫穗槐-4, 11-二烯氧化酶基因、細(xì)胞色素P450氧化還

原酶基因、青蒿醛雙鍵還原酶和醛脫氫酶基因進(jìn)行了重點(diǎn)介紹。此外, 本綜述針對(duì)近年來(lái)青蒿素合成生物學(xué)發(fā)

展的特點(diǎn)以及影響底盤細(xì)胞制備目的產(chǎn)物的因素進(jìn)行了詳細(xì)的論述。

關(guān)鍵詞: 青蒿素; 天然藥物合成生物學(xué); 底盤細(xì)胞; 模塊; 元件

中圖分類號(hào): R931 文獻(xiàn)標(biāo)識(shí)碼: A 文章編號(hào): 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

?青蒿素是一種非常優(yōu)良的抗瘧藥物, 存在活性好、毒副作用小、市場(chǎng)需求大、來(lái)源窄等特點(diǎn), 從而 導(dǎo)致價(jià)格昂貴 , 不利于疾病的治療和預(yù)防, 嚴(yán)重影響收稿日期: 2012-11-20; 修回日期: 2012-12-15. 人類的健康安全。因此, 需要建立一種大規(guī)模的、廉基金項(xiàng)目: 國(guó)家自然科學(xué)基金資助項(xiàng)目 (30701061).

*通訊作者 Tel: 86-10-63165169, Fax: 86-10-63165197,

E-mail: jianqiangk@imm.ac.cn 價(jià)生產(chǎn)這種藥物的替代方法。現(xiàn)在看來(lái), 天然藥物合成生物技術(shù)無(wú)疑是最理想的。

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