Disruption of the Ergosterol Biosynthetic Pathway Results in Increased Membrane Permeability, Causing Overproduction and Secretion of Extracellular Monascus Pigments in Submerged Fermentation.

Because Monascus pigments (MPs) predominantly accumulate in the cytoplasm during submerged fermentation, many biotechnologies are applied to enhance the production of extracellular MPs (exMPs) to reduce the downstream processing costs. In this study, the genes monascus_7017 and monascus_8018, identified as ERG4 genes, were knocked out to disrupt the ergosterol biosynthetic pathway and enhance the production of exMPs in Monascus purpureus LQ-6. Double-deletion of EGR4 in M. purpureus LQ-6 reduced ergosterol concentration by 57.14% and enhanced exMP production 2.06-fold. In addition, integrated transcriptomic and proteomic analyses were performed to elucidate the transmembrane secretion mechanism of exMPs based on the relationship between ergosterol synthesis and membrane permeability, which revealed that several metabolic pathways were noticeably dynamic, including fatty acid degradation, amino acid metabolism, energy metabolism, carbohydrate metabolism, and transport. These findings therefore clarified the secretion mechanism of exMPs and provide a novel strategy for further enhancement of exMP production in submerged fermentation.