The hadal biosphere is the most mysterious ecosystem on the planet, located in a unique and extreme environment on Earth. To adapt to extreme environmental conditions, hadal microorganisms evolve special strategies and metabolisms to survive and reproduce. However, the secondary metabolites of the hadal microorganisms are poorly understood. In this study, we focused on the isolation and characterization of hadal fungi, screening the potential strains with bioactive natural products. The isolates obtained were detected further for the polyketide synthase (PKS) genes. Two isolates of Alternaria alternata were picked up as the representatives, which had the potential to synthesize active natural products. The epigenetic modifiers were used for the two A. alternata isolates to stimulate functional gene expression in hadal fungi under laboratory conditions. The results showed that the chemical epigenetic modifier, 5-Azacytidine (5-Aza), affected the phenotype, PKS gene expression, production of secondary metabolites, and antimicrobial activity of the hadal fungus A. alternata. The influence of epigenetic modification on natural products was strongest when the concentration of 5-Aza was 50 mu M. Furthermore, the modification of epigenetic agents on hadal fungi under high hydrostatic pressure (HHP) of 40 MPa displayed significant effects on PKS gene expression, and also activated the production of new compounds. Our study demonstrates the high biosynthetic potential of cultivable hadal fungi, but also provides evidence for the utility of chemical epigenetic modifiers on active natural products from hadal fungi, providing new ideas for the development and exploitation of microbial resources in extreme environments.
