Activation of the Dimer of 3, 4‐dimethylphenol Production From Marine <i>Streptomyces</i> sp. FJNU027 Under Oligotrophic Condition

Activating cryptic secondary metabolic gene clusters is a critical area of research in Streptomyces, and the cultivation-based approach is one of effective ways to induce the expression of cryptic gene clusters. In this study, the oligotrophic medium and modified Gauze's medium were used to culture the marine Streptomyces sp. FJNU027 strain, and a unique secondary metabolite in oligotrophic culture was found by HPLC assay when compared with the modified Gauze's culture. Then the differential product was isolated through large-scale fermentation, solvent extraction, column chromatography over Sephadex LH-20, and HPLC preparation. The pure differential product was analyzed by NMR and LC-MS, and identified as 4,4',5,5'-tetramethyl-[1,1'- diphenyl]-2,2'-diol. To elucidate the possible biosynthesis mechanism of the differential product, the transcriptome sequencing was performed. It showed the expressions of polyketide synthase gene (FZ01GL006410) and cytochrome P450 gene (FZ01GL006417) were significantly enhanced in the oligotrophic medium, and these two genes might be responsible for the biosynthesis of the differential product. This compound was reported for the first time isolated from a natural source, demonstrating a novel approach for acquiring this type of compound. The results indicate that oligotrophic culture is an effective method for modulating the secondary metabolism of Streptomyces.