Selective production of epothilone B by heterologous expression of propionyl-CoA synthetase in Sorangium cellulosum.
The metabolic engineering of epothilones, as secondary metabolites, was investigated using Sorangium cellulosum to achieve the selective production of epothilone B, a potent anticancer agent. Thus, the propionyl-CoA synthetase gene (prpE) from Ralstonia solanacearum was heterologously expressed in S. cellulosum to increase the production of epothilone B. Propionyl-CoA synthetase converts propionate into propionyl-CoA, a potent precursor of epothilone B. The recombinant S. cellulosum containing the prpE gene exhibited a significant increase in the resolution of epothilones B/A, with an epothilone B to A ratio of 127 to 1, which was 100 times higher than that of the wild-type cells, demonstrating its potential use for the selective production of epothilone B.
Han
Se Jong
SJ
Department of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Korea.
Park
Sang Woo
SW
Park
Byung Woo Kim
BW
Sim
Sang Jun
SJ
D000214:Acyl Coenzyme A / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism*; D001709:Biotechnology / Q000379:methods; D003066:Coenzyme A Ligases / Q000235:genetics* / Q000378:metabolism*; D003470:Culture Media; D034261:Epothilones / Q000096:biosynthesis* / Q000737:chemistry; D005818:Genetic Engineering / Q000379:methods; D009231:Myxococcales / Q000201:enzymology* / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D043368:Ralstonia solanacearum / Q000201:enzymology* / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D000214:Acyl Coenzyme A; D000970:Antineoplastic Agents; D003470:Culture Media; D034261:Epothilones; D011994:Recombinant Proteins; C009061:propionyl-coenzyme A; D003066:Coenzyme A Ligases; C068072:propionate - CoA ligase; C093788:epothilone B