[Biosynthesis of amorpha-4,11-diene, a precursor of the antimalarial agent artemisinin, in Escherichia coli through introducing mevalonate pathway].

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