Functional characterization of mpdh as a key dehydratase in citrinin biosynthesis in M. purpureus YY-1

Monascus spp., a traditional fermentation microorganism, produces natural pigments but also citrinin, a nephrotoxic mycotoxin. This study investigated the function of mpdh in M. purpureus YY-1, which encodes a dehydratase. Following fermentation, the Δmpdh strain exhibited increased biomass compared to the wild-type strain YY-1, along with a 79.3 % reduction in citrinin production and a 31.4 % decrease in Monascus azaphilone pigments (MonAzPs) yield. Transcriptomic analysis revealed downregulation of differentially expressed genes (DEGs) within the citrinin biosynthesis cluster, particularly those associated with polyketide synthase. The disruption of mpdh function altered key primary metabolic pathways, reducing acetyl-CoA levels and consequently impairing citrinin and MonAzPs biosynthesis. The redistribution of acetyl-CoA from secondary metabolism to energy metabolism for mycelial growth resulted in enhanced biomass in the Δmpdh strain. These results confirm that mpdh catalyzes the dehydration of Intermediate 6 to drive citrinin synthesis, establishing its pivotal role in the citrinin biosynthetic pathway.