Positive regulation of the MarR-type regulator slnO and improvement of salinomycin production by by multiple transcriptional regulation.

The purpose of this study was to explore the function of the MarR family regulator slnO. Additionally, a high-yield strain of salinomycin was constructed using combined regulation strategies. First, the gene overexpression strain (GO) was constructed in . Compared to the wild-type (WT) strain, salinomycin production in the GO strain increased by approximately 28%. Electrophoretic mobility gel shift assays (EMSAs) confirmed that the SlnO protein can bind specifically to the intergenic regions of , , and . qRT-PCR experiments also showed that , , and were significantly upregulated, whereas the expression level of the gene was downregulated in the GO strain. Second, the gene deletion strain (slnNDM) was used as the starting strain, and the pathway-specific gene in the salinomycin gene cluster was overexpressed in slnNDM. This new strain was named ZJUS01. The yield of salinomycin in the ZJUS01 strain was 25% and 56% higher than those in the slnNDM and WT strains, respectively. The above results indicate that the gene has a positive regulatory effect on the biosynthesis of salinomycin. Meanwhile, the yield of salinomycin can be greatly increased by manipulating multiple transcriptional regulations.