Integrated physiology, transcriptomics and targeted metabolomics reveal a potential quorum sensing network involved in the initial spore density-dependent regulation of morphogenesis and polyketide biosynthesis in Monascus.

Density dependence is a key characteristic of quorum sensing (QS) in fungi; however, no relevant reports have been found in Monascus. Therefore, this study aimed to investigate the effects of initial spore density on the morphological development and polyketide secondary metabolism of Monascus purpureus to elucidate the regulatory role of QS. At the high initial spore density, more active conidial development and secondary metabolism were observed in the early fermentation stage, accompanied by rougher hyphal surfaces, increased secretion and larger vacuoles. Gene set enrichment analysis (GSEA) based on transcriptomic data revealed that high initial spore density activated ribosome biosynthesis to support rapid cell growth and secondary metabolism, whereas low initial spore density upregulated genes associated with peroxisome biosynthesis, the enzymatic antioxidant system, fatty acid degradation, fatty acid biosynthesis, and asexual sporulation. Furthermore, the reduction in linoleic acid content at high initial spore density suggested that linoleic acid and its derivatives may function as putative quorum sensing molecules (QSMs). Finally, a potential regulatory network integrating initial spore density with secondary metabolism and development was proposed. These findings enhance the understanding of the QS network in Monascus and offer a theoretical basis for the optimization of fermentation processes.