Efficient Production of Natural Yellow Azaphilone Pigments from <i>Monascus purpureus</i> Regulated by Microparticle-Triggered Stress

Interaction with inert substances can profoundly affect the biosynthesis of metabolites in microorganisms. Here, we show that SiO₂ microparticles cause changes in the cell morphology of <i>Monascus purpureus</i>. SiO₂ also more than doubles the titer of yellow azaphilone pigments (YAzPs), reaching 788 U/mL. Transcriptomic and metabolomic analyses revealed that SiO₂ microparticles modulated the expression of a large variety of genes and the production of key metabolites. In addition to upregulating the genes directly involved in YAzPs biosynthesis, the presence of SiO₂ modulated the expression of key genes and the activities of key enzymes involved in calcium signaling and reactive oxygen species (ROS) response pathways. Together with SiO₂-caused membrane damage, these changes are in accord with elevated levels of Ca²⁺ and ROS within the cells, as observed through specific reporters and validated by using inhibitors targeting these pathways. This research improves our understanding of the effects of inert substances on microbial metabolism.