Developing <i>Escherichia coli</i> MG1655 as a Microbial Cell Factory for Sustainable Gadusol Biosynthesis

Gadusol, a potent natural compound with both UV-absorbing and antioxidant properties, is found in various aquatic organisms, notably the zebrafish. It holds considerable promise for applications in cosmetics, pharmaceuticals, and the food industry. However, its natural extraction yields are extremely low and environmentally unsustainable. In this study, we engineered Escherichia coli MG1655 to produce the natural sunscreen gadusol. This was achieved by heterologously expressing the key biosynthetic genes (eevs and mt-ox) via plasmid-based or chromosomal integration strategies. To enhance precursor supply, we subsequently engineered the pentose phosphate pathway by deleting competitive pathway genes and overexpressing pathway enzymes, thereby increasing the flux toward sedoheptulose-7-phosphate. The final optimized strain, featuring a stable, plasmid-free genomic integration, produced gadusol at titers of 668.09 mg/L and 2.43 g/L in shake-flask and fed-batch fermentation, respectively, representing a significant titer for sustainable production and potential industrial applications.