[Biosynthesis of amorpha-4,11-diene, a precursor of the antimalarial agent artemisinin, in Escherichia coli through introducing mevalonate pathway].
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.
College of Life Science, Fujian Normal University, Fuzhou 350108, China
Tao
T
Wu
Shengming
S
Wu
Qing
Q
Yin
Hongmei
H
Dai
Shulong
S
Li
Fangting
F
Dong
Bilian
B
Chen
Hongqing
H
Fang
D019883:Alkyl and Aryl Transferases / Q000235:genetics; D000962:Antimalarials / Q000378:metabolism*; D037621:Artemisinins / Q000378:metabolism*; D013293:Enterococcus faecalis / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D060847:Metabolic Engineering / Q000379:methods*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000378:metabolism*; D014169:Transformation, Bacterial
D000962:Antimalarials; D037621:Artemisinins; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C515348:amorpha-4,11-diene; D019883:Alkyl and Aryl Transferases; C403714:amorpha-4,11-diene synthase; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase