Biosynthesis and Microbial Production of Carminic Acid: From Pathway Elucidation to Synthetic Biology.

Carminic acid (CA) is a high-value natural anthraquinone pigment used in foods, cosmetics, textiles, and pharmaceuticals, but its current industrial supply depends largely on extraction from the scale insect Dactylopius coccus, creating constraints in yield, cost, sustainability, and allergen control. This review summarizes recent progress from pathway elucidation to microbial production. We first outline the structure, occurrence, applications, and biosynthetic logic of CA, emphasizing the convergence of type III polyketide assembly with insect-associated tailoring reactions, especially C-glycosylation. We then compare heterologous production strategies in Escherichia coli, Saccharomyces cerevisiae, Yarrowia lipolytica, and Aspergillus nidulans, focusing on chassis-specific advantages, bottlenecks, precursor supply, malonyl-CoA engineering, dynamic regulation, enzyme compatibility, compartmentalization, and downstream processing. Structurally related anthraquinone pigments are further discussed to extract broader design principles for pathway diversification and synthetic biology. Finally, we highlight key challenges for industrial translation, including low titers, incomplete enzyme characterization, host-pathway incompatibility, and scalable purification, and propose integrated strategies combining precursor-pathway rewiring, AI-assisted enzyme engineering, biosensor-based regulation, and process optimization to develop competitive microbial cell factories.