Inactivation of the genes involved in histone H3-lysine 4 methylation abates the biosynthesis of pigment azaphilone in Monascus purpureus

Diand tri-methylation of lysine 4 on histone H3 (H3K4me2 and H3K4me3, respectively) are epigenetic markers of active genes. Complex associated with Set1 (COMPASS) mediates these H3K4 methylations. The involvement of COMPASS activity in secondary metabolite (SM) biosynthesis was first demonstrated with an Aspergillus nidulans cclA knockout mutant. The cclA knockout induced the transcription of two cryptic SM biosynthetic gene clusters, leading to the production of the cognate SM. Monascus spp. are filamentous fungi that have been used for food fermentation in eastern Asia, and the pigment Monascus azaphione (MAz) is their main SM. Monascus highly produces MAz, implying that the cognate biosynthetic genes are highly active in transcription. In the present study, we examined how COMPASS activity modulates MAz biosynthesis by inactivating Monascus purpureus cclA (Mp-cclA) and swd1 (Mpswd1). For both ΔMp-cclA and ΔMp-swd1, a reduction in MAz production, accompanied by an abated cell growth, was observed. Suppression of MAz production was more effective in an agar culture than in the submerged liquid culture. The fidelity of the ΔMp-swd1 phenotypes was verified by restoring the WT-like phenotypes in a reversion recombinant mutant, namely, trpCp: Mp-swd1, that was generated from the ΔMp-swd1 mutant. Realtime quantitative Polymerase chain reaction analysis indicated that the transcription of MAz biosynthetic genes was repressed in the ΔMp-swd1 mutant. This study demonstrated that MAz biosynthesis is under the control of COMPASS activity and that the extent of this regulation is dependent on growth conditions.