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.