Activation of 3, 4-dimethylphenol dimer production from marine Streptomyces sp. FJNU027 under oligotrophic condition

Activating the cryptic secondary metabolic gene clusters is a vital research field in Streptomyces. The marine Streptomyces sp. FJNU027 strain which could produce tirandamycins was cultured in the oligotrophic medium. Compared with normal medium, a differential product in oligotrophic culture was found by HPLC assay. After mass fermentation, 2 mg of the differential product was obtained from 30 L fermentation broth by solvent extraction, column chromatography over sephadex LH-20 and reverse phase C18, and other methods. It was identified as 4,4',5,5'-tetramethyl-[1,1'- diphenyl]-2,2'-diol by NMR and MS data. The production of this compound was enhanced with the increment of cultural time. Transcriptome sequencing analysis showed that the highest upregulated genes under oligotrophic condition were glycosidase, TraR/DksA C4-type zinc finger protein and ribonuclease encoding genes, while the expression of a MarR family transcriptional regulator was most significantly decreased under oligotrophic condition. The results indicate that oligotrophic culture is an effective method for altering the secondary metabolism of Streptomyces. Overall design: To investigate the possible mechanism for the activation of differential product in oligotrophic medium, we performed gene expression profiling analysis using data obtained from RNA-seq of one strain in two different media. Comparative gene expression profiling analysis of RNA-seq data for the strain cultured on oligotrophic medium and modified Gauze's medium.