Significant enhancement of edible Monascus azaphilone pigments production via targeted improvement of the expression of histone deacetylase MrHos2

Monascus azaphilone pigments (MonAzPs) are beneficial secondary metabolites secreted by Monascus spp., which have great potentials to be used in industrial fields besides food industry. But there is very little knowledge about their regulatory mechanism, which limits the large-scale production and utilization of MonAzPs. In this study, we firstly studied the effect on MonAzPs production by inhibiting and enhancing histone deacetylase gene hos2 (Mrhos2) expression in Monascus ruber. UPLC detection revealed that inactivation of Mrhos2 dramatically decreased MonAzPs production, while overexpression of Mrhos2 significantly increased MonAzPs production. Transcriptional level analysis shows Mrhos2 regulates expression of MonAzPs biosynthesis genes. Immunoaffinity enrichment assisted mass spectrometry assay reveals deletion of Mrhos2 perturbs lysine acetylation of enzymes in the metabolic pathway of acetyl-CoA and malonyl-CoA. Collectively, transcription activation and protein acetylation modification mediated by MrHos2 are involved in regulating the MonAzPs production, and MrHos2 can be used as a target to increase MonAzPs production.