Improvement of spinosad production by overexpression of gtt and gdh controlled by promoter PermE* in Saccharopolyspora spinosa SIPI-A2090.
Spinosyns A and D are novel macrolide secondary metabolites containing two deoxysugars. Each of the sugars is derived from a common intermediate, which is biosynthesized sequentially by NDP-glucose synthase and glucose dehydratase. Systematical duplication of gtt and gdh was carried out by genetic engineering in Saccharopolyspora spinosa. Introduction of additional gtt and gdh genes under the control of PermE* promoter showed significant increase on their transcript levels. The production of spinosad was increased by over threefold to reach 800 μg/ml in the recombinant strain SIPI-M2093.
State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, Shanghai, China.
Hai-Xue
HX
Pan
Ji-An
JA
Li
Ning-Jun
NJ
He
Ji-Ye
JY
Chen
Yu-Meng
YM
Zhou
Lei
L
Shao
Dai-Jie
DJ
Chen
D001709:Biotechnology; D004338:Drug Combinations; D020440:Gene Duplication; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D042843:Glucose 1-Dehydrogenase / Q000235:genetics / Q000378:metabolism; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism; D018942:Macrolides / Q000378:metabolism*; D015394:Molecular Structure; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016930:Saccharopolyspora / Q000235:genetics / Q000378:metabolism
D004338:Drug Combinations; D018942:Macrolides; D042843:Glucose 1-Dehydrogenase; D006836:Hydro-Lyases; C436310:NDP-glucose dehydratase; C415329:spinosad