Biodiversity and metabolite richness of endophytic fungi are highly fascinating. Some of them have even been reported to have the shared biosynthetic basis for the production of plant specific metabolites. However, only limited reports are there on enhancement of production of plant specific metabolites from endophytic fungi. In the study, endophytic Diaporthe sp. PF20 from Piper nigrum L. was identified to have the ability to produce piperine by liquid chromatography tandem mass spectroscopy. The isolate PF20 was further subjected to epigenetic treatment along with previously characterized piperine producing Colletotrichum sp. and Mycosphaerella sp. from the same plant. Very interestingly, use of histone deacetylase inhibitor suberohydroxamic acid enhanced the piperine production in PF20. Here, the epigenetic modulator mediated enhancement of phytochemical biosynthetic potential of endophytic fungi is novel in its approach. Hence the results of the study open up new avenues to maintain the biosynthetic competency of endophytic fungi, which is highly challenging. Even though piperine production has previously been reported from endophytic fungi, epigenetic modulator mediated multiplexing of this property as observed for PF20 is highly attractive. This is because, only this organism was found to be susceptible to epigenetic modulation based piperine enhancement among the selected isolates.