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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.
Asunto(s)
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

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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