Biosynthesis of complex polyketides in a metabolically engineered strain of E. coli.
The macrocyclic core of the antibiotic erythromycin, 6-deoxyerythronolide B (6dEB), is a complex natural product synthesized by the soil bacterium Saccharopolyspora erythraea through the action of a multifunctional polyketide synthase (PKS). The engineering potential of modular PKSs is hampered by the limited capabilities for molecular biological manipulation of organisms (principally actinomycetes) in which complex polyketides have thus far been produced. To address this problem, a derivative of Escherichia coli has been genetically engineered. The resulting cellular catalyst converts exogenous propionate into 6dEB with a specific productivity that compares well with a high-producing mutant of S. erythraea that has been incrementally enhanced over decades for the industrial production of erythromycin.
Pfeifer
B A
BA
Department of Chemical Engineering, Stanford University, Stanford, CA 94305-5025, USA.
Admiraal
S J
SJ
Gramajo
H
H
Cane
D E
DE
Khosla
C
C
D000214:Acyl Coenzyme A / Q000378:metabolism; D001426:Bacterial Proteins; D003001:Cloning, Molecular; D004917:Erythromycin / Q000031:analogs & derivatives / Q000096:biosynthesis*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics*; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016930:Saccharopolyspora / Q000201:enzymology / Q000235:genetics*; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics / Q000378:metabolism; D014169:Transformation, Bacterial
D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; D009097:Multienzyme Complexes; D011993:Recombinant Fusion Proteins; C082662:phosphopantetheinyl transferase; C015357:methylmalonyl-coenzyme A; C034277:6-deoxyerythronolide B; D004917:Erythromycin; D017855:Transferases (Other Substituted Phosphate Groups)