Biosynthesis of valuable blue pigments: Recent advances, applications and perspectives

Blue pigments occupy a unique niche in the natural colorant market, offering cool-toned hues that cannot be substituted by commonly used carotenoid-derived reds and yellows. Their expanding applications in food, textiles, biomedicine and materials science have stimulated growing academic and industrial interests. However, the large-scale production of natural blue pigments remains hindered by limited natural sources and inefficient microbial biosynthesis. This review focuses specifically on four representative microbial blue pigment systems: violacein, indigo, indigoidine and phycocyanobilin. Their production is often constrained by restricted pathway flux, limited precursor availability and product-associated toxicity, particularly that arising from the accumulation of hydrophobic pigments. Based on the analysis of their biosynthetic pathways and properties, strategies addressing these bottlenecks are organized into pathway optimization, precursor engineering, and membrane engineering, with their applicability and limitations compared across the four systems. Finally, pigment-specific applications of these pigments in dyeing, therapeutic development and emerging bioelectronics were also summarized. Overall, by integrating shared production bottlenecks with pigment-specific characteristics, this review provides a focused comparative framework for selecting suitable engineering strategies and may offer transferable design principles for other pigments.