Positive regulation of MarR-type regulator slnO and improving salinomycin production of Streptomyces albus by multiple transcriptional regulations
The purpose of this study is to explore the function of MarR-family regulator slnO. In addition, the high-yield strain of salinomycin was constructed by using combined regulation strategies. Firstly the slnO gene over-expression strain (GO) was constructed in Streptomyces albus. Compared to wild type (WT) strain,salinomycin production in GO strain was increased about 28%. Electrophoretic mobility gel shift assays (EMSAs) confirmed that SlnO protein can bind specifically to the intergenic region of slnN-slnO, slnQ-slnA1 and slnF-slnT. qRT-PCR experiments also showed that slnA1, slnF, and slnT1 were significantly up-regulated, while the expression level of the slnN gene was down-regulated in GO strain. Secondly, slnN gene deletion strain (slnNDM) was used as the starting strain, and the pathway specific gene slnR in salinomycin gene cluster was over expressed in slnNDM. The new strain was named ZJUS01. The yield of salinomycin in ZJUS01 strain was 25% and 56% higher than that in slnNDM strain and WT strain. Above results indicate that the slnO gene has a positive regulation effect on the biosynthesis of salinomycin. Meanwhile, the yield of salinomycin could be greatly increased by manipulating multiple transcriptional regulations.