Abstract: Various secondary metabolites produced by filamentous fungi, especially Penicillium, are becoming an important source of new drugs. Many drugs such as anticancer drugs, antibiotics, and immunosuppressants are derived from fungal secondary metabolites. However, the secondary metabolism of fungi is affected by many factors, among which epigenetic modification plays an important regulatory role. The epigenetic modification by histone acetylation is often associated with transcriptional activation, thereby facilitating the synthesis of secondary metabolites. In this study, Penicillium christenseniae SD-193.84 was used as the research object. Bioinformatics methods were used to identify the histone deacetylase(HDAC) gene. A gene knockout technique based on homologous recombination was established in this fungus to knock out HDAC. Analysis of secondary metabolites was conducted before and after the gene knockout. We found that HDAC affects the synthesis of a variety of secondary metabolites in the fungus. This study provides a reference for molecular genetic manipulation and secondary metabolic regulation in Penicillium.

Key words: histone deacetylase, Penicillium, epigenetic modification, secondary metabolites;gene knockout