Biosynthesis of amorpha-4,11-diene, a precursor of the antimalarial agent artemisinin, in Escherichia coli through introducing mevalonate pathway.
- Author:
Tao WU
1
;
Shengming WU
;
Qing YIN
;
Hongmei DAI
;
Shulong LI
;
Fangting DONG
;
Bilian CHEN
;
Hongqing FANG
Author Information
1. College of Life Science, Fujian Normal University, Fuzhou 350108, China
- Publication Type:Journal Article
- MeSH:
Alkyl and Aryl Transferases;
genetics;
Antimalarials;
metabolism;
Artemisinins;
metabolism;
Enterococcus faecalis;
genetics;
Escherichia coli;
genetics;
metabolism;
Metabolic Engineering;
methods;
Phosphotransferases (Alcohol Group Acceptor);
metabolism;
Sesquiterpenes;
metabolism;
Transformation, Bacterial
- From:
Chinese Journal of Biotechnology
2011;27(7):1040-1048
- CountryChina
- Language:Chinese
-
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.
