%0 Journal Article
%T Biosynthesis of amorpha-4,11-diene, a precursor of the antimalarial agent artemisinin, in Escherichia coli through introducing mevalonate pathway<br>在大肠杆菌内引入甲羟戊酸途径高效合成抗疟药青蒿素前体——紫穗槐-4,11-二烯
%A Tao Wu
%A Shengming Wu
%A Qing Yin
%A Hongmei Dai
%A Shulong Li
%A Fangting Dong
%A Bilian Chen
%A Hongqing Fang
%A <br>吴涛
%A 吴胜明
%A 殷晴
%A 戴红梅
%A 李树龙
%A 董芳庭
%A 陈必链
%A 方宏清
%J 生物工程学报
%D 2011
%I 
%X Artemisinin-based combination therapies (ACTs) are recommended to be the most effective therapies for the first-line treatment of uncomplicated falciparum malaria. However, artemisinin is often in short supply and unaffordable to most malaria patients, which limits the wide use of ACTs. Production of amorpha-4,11-diene, an artemisinin precursor, was investigated by engineering a heterologous isoprenoid biosynthetic pathway in Escherichia coli. The production of amorpha-4,11-diene was achieved by expression of a synthetic amorpha-4,11-diene synthase gene in Escherichia coli DHGT7 and further improved by about 13.3 fold through introducing the mevalonate pathway from Enterococcus faecalis. After eliminating three pathway bottlenecks including amorpha-4,11-diene synthase, HMG-CoA reducase and mevalonate kinase by optimizing the metabolic flux, the yield of amorpha-4,11-diene was increased by nearly 7.2 fold and reached at 235 mg/L in shaking flask culture. In conclusion, an engineered Escherichia coli was constructed for high-level production of amorpha-4,11-diene.
%K amorpha-4
%K 11-diene
%K artemisinin
%K mevalonate pathway
%K metabolic regulation
%K biosynthesis<br>紫穗槐-4
%K 11-二烯，青蒿素，甲羟戊酸途径，代谢调控，代谢调控，生物合成
%U http://www.alljournals.cn/get_abstract_url.aspx?pcid=90BA3D13E7F3BC869AC96FB3DA594E3FE34FBF7B8BC0E591&jid=A66E90C274451689E69F6F0291467824&aid=08FC36D46A3865B24F4E257B3D520D06&yid=9377ED8094509821&vid=DB817633AA4F79B9&iid=DF92D298D3FF1E6E&sid=FC27EB98080C89E6&eid=94D812A784CFA7CC&journal_id=1000-3061&journal_name=生物工程学报&referenced_num=1&reference_num=21