Abstract |
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.
|
Authors | Tao Wu, Shengming Wu, Qing Yin, Hongmei Dai, Shulong Li, Fangting Dong, Bilian Chen, Hongqing Fang |
Journal | Sheng wu gong cheng xue bao = Chinese journal of biotechnology
(Sheng Wu Gong Cheng Xue Bao)
Vol. 27
Issue 7
Pg. 1040-8
(Jul 2011)
ISSN: 1000-3061 [Print] China |
PMID | 22016988
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antimalarials
- Artemisinins
- Polycyclic Sesquiterpenes
- Sesquiterpenes
- amorpha-4,11-diene
- Alkyl and Aryl Transferases
- amorpha-4,11-diene synthase
- Phosphotransferases (Alcohol Group Acceptor)
- mevalonate kinase
|
Topics |
- Alkyl and Aryl Transferases
(genetics)
- Antimalarials
(metabolism)
- Artemisinins
(metabolism)
- Enterococcus faecalis
(genetics)
- Escherichia coli
(genetics, metabolism)
- Metabolic Engineering
(methods)
- Phosphotransferases (Alcohol Group Acceptor)
(metabolism)
- Polycyclic Sesquiterpenes
- Sesquiterpenes
(metabolism)
- Transformation, Bacterial
|