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.
Artículo
en Chino
| 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.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Sesquiterpenos
/
Transformación Bacteriana
/
Enterococcus faecalis
/
Fosfotransferasas (Aceptor de Grupo Alcohol)
/
Transferasas Alquil y Aril
/
Artemisininas
/
Escherichia coli
/
Ingeniería Metabólica
/
Genética
/
Metabolismo
Idioma:
Chino
Revista:
Chinese Journal of Biotechnology
Año:
2011
Tipo del documento:
Artículo
Similares
MEDLINE
...
LILACS
LIS