Conclusion

The results of DEG analysis and functional validation demonstrate that the Hup A biosynthetic pathway in endophytic fungus C.gloeosporioides Cg01 might be different from that proposed in plants.The Hup A-biosynthesis genes in endophytic fungi might co-evolve with the plant machinery rather than being acquired through HGT.The HMT genes(CgClr4)and HDAC genes(CgClr3，CgSir2-6)associated with histone modification were involved in the regulation of Hup A biosynthesis.This is the first report on epigenetic modification analysis in high value SM-producing endophytic fungi.These findings shed new light on Hup A biosynthesis and regulation by Hup A-producing endophytic fungi，and it is crucial for larger production of Hup A from fungi.

Abbreviations(https://www.daowen.com)

PCGs：protein-coding genes；ML：maximum likelihood；DEGs：differentially expressed genes；LDC：lysine decarboxylase；CAO：copper amine oxidase；PKS：polyketides synthases；BBE：berberine bridge enzyme；2OGD：2-oxoglutarate-dependent dioxygenases；HGT：horizontal gene transfer；HAT：histone acetyltransferase；HMT：histone methyltransferase；HDAC：histone deacetylase；NCBI RefSeq：National Center of Biotechnology Information Reference Sequence；UniProt KB：UniProt Knowledgebase；GO：Gene ontology；KEGG：Kyoto Encyclopedia of Genes and Genomes；KOG：Eu Karyotic Orthologous Groups；HPLC：High Performance Liquid Chromatography.