Biosynthesis of amorpha-4,11-diene, a precursor of the antimalarial agent artemisinin, in Escherichia coli through introducing mevalonate pathway / 生物工程学报
Chinese Journal of Biotechnology
;
(12): 1040-1048, 2011.
Article
in Chinese
| WPRIM
| ID: wpr-324505
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Sesquiterpenes
/
Transformation, Bacterial
/
Enterococcus faecalis
/
Phosphotransferases (Alcohol Group Acceptor)
/
Alkyl and Aryl Transferases
/
Artemisinins
/
Escherichia coli
/
Metabolic Engineering
/
Genetics
/
Metabolism
Language:
Chinese
Journal:
Chinese Journal of Biotechnology
Year:
2011
Type:
Article
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