Metabolic engineering of Streptomyces venezuelae for malonyl-CoA biosynthesis to enhance heterologous production of polyketides.
Using metabolic engineering, we developed Streptomyces venezuelae YJ028 as an efficient heterologous host to increase the malonyl-CoA pool to be directed towards enhanced production of various polyketides. To probe the applicability of newly developed hosts in the heterologous production of polyketides, we expressed type III polyketide synthase, 1,3,6,8-tetrahydroxynaphthalene synthase, in these hosts. Flaviolin production was doubled by expression of acetyl-CoA carboxylase (ACCase) and 4-fold by combined expression of ACCase, metK1-sp and afsR-sp. Thus, the newly developed Streptomyces venezuelae YJ028 hosts produce heterologous polyketides more efficiently than the parent strain.
Department of Pharmaceutical Engineering, Institute of Biomolecule Reconstruction, Sun Moon University, Tangjeonmyun, Asansi, Chungnam 336-708, Republic of Korea.
Sushila
S
Maharjan
Je Won
JW
Park
Yeo Joon
YJ
Yoon
Hei Chan
HC
Lee
Jae Kyung
JK
Sohng
D024861:Genetic Enhancement / Q000379:methods*; D018942:Macrolides / Q000378:metabolism*; D008316:Malonyl Coenzyme A / Q000096:biosynthesis* / Q000235:genetics; D055442:Metabolome / Q000502:physiology*; D015202:Protein Engineering / Q000379:methods*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013302:Streptomyces / Q000502:physiology*
D018942:Macrolides; D011994:Recombinant Proteins; D008316:Malonyl Coenzyme A