Growth-coupled microbial biosynthesis of the animal pigment xanthommatin.

Summary

The authors introduce a growth-coupled biosynthetic strategy that links restoration of C1 metabolism to pigment output, enabling gram-scale microbial production of xanthommatin in Pseudomonas putida. Adaptive laboratory evolution further increased yields, suggesting a generalizable, plug-and-play approach for natural product biomanufacturing.

Key Findings

• Developed a growth-coupled biosynthetic strategy that uses C1 restoration to drive pigment synthesis.
• Enabled microbial xanthommatin production in a 5,10-methylenetetrahydrofolate auxotroph of Pseudomonas putida.
• Formate released during xanthommatin synthesis relieved C1 deficiency, coupling growth to production.
• Adaptive laboratory evolution achieved gram-scale production from glucose.

Clinical Implications

Although preclinical, the platform could enable supply of biobased pigments with improved safety and sustainability profiles for dermatologic and cosmetic applications, reducing reliance on petrochemical dyes.

Limitations

• Demonstrated in a single chassis organism and pigment; generalizability to other pathways needs validation
• No evaluation of downstream formulation, safety, or stability in cosmetic end-use

Future Directions

Extend growth-coupled strategies to additional natural products, scale bioprocesses, and assess pigment safety, stability, and performance in cosmetic formulations.