Engineering a regulatory region of jadomycin gene cluster to improve jadomycin B production in Streptomyces venezuelae.
Streptomyces venezuelae ISP5230 produces a group of jadomycin congeners with cytotoxic activities. To improve jadomycin fermentation process, a genetic engineering strategy was designed to replace a 3.4-kb regulatory region of jad gene cluster that contains four regulatory genes (3' end 272 bp of jadW2, jadW3, jadR2, and jadR1) and the native promoter upstream of jadJ (P(J)) with the ermEp* promoter sequence so that ermEp* drives the expression of the jadomycin biosynthetic genes from jadJ in the engineered strain. As expected, the mutant strain produced jadomycin B without ethanol treatment, and the yield increased to about twofold that of the stressed wild-type. These results indicated that manipulation of the regulation of a biosynthetic gene cluster is an effective strategy to increase product yield.
Zheng
Jian-Ting
JT
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, P. O. Box 2714, Beijing, 100081, People's Republic of China.
Wang
Sheng-Lan
SL
Yang
Ke-Qian
KQ
D001483:Base Sequence; D015139:Blotting, Southern; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D005818:Genetic Engineering / Q000379:methods*; D007546:Isoquinolines / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*; D014170:Transformation, Genetic
D004269:DNA, Bacterial; D007546:Isoquinolines; C081750:jadomycin B