Enhancing melatonin biosynthesis in crops through synthetic genetic circuits: A strategy for nutritional fortification in soybean and stress resistance in cotton

Melatonin has gained considerable prominence in the treatment of insomnia that significantly impacts one-third of the global population. The production of melatonin remains challenging due to limitations in current methods. Thus, there is an urgent need for developing more efficient and innovative production techniques. Here, we demonstrated the potential of crop seeds as a platform for melatonin synthesis by engineering multiple BUFFER genetic circuits using synthesized transcriptional regulators, which enhance expression precision, orthogonality and thresholds. Biofortified soybeans exhibited a 31-fold increase in melatonin content compared to standard Williams 82, without detrimental impact on yield. Protein content was elevated, oil content reduced and the soybeans were suitable for post-harvest processing. Furthermore, plants enriched in endogenous melatonin exhibited stronger resilience to adversity, evidenced by improved salinity tolerance in soybean seeds and increased resistance to Verticillium dahliae in cotton. Our research paves the way for the synthesis of target compounds in staple crops using synthetic genetic circuits, facilitating the development of novel biofortified crops to increase nutritional availability and environmental adaptability in the upcoming new era of agriculture.