Melatonin biosynthesis pathways in nature and its production in engineered microorganisms

Melatonin is a biogenic amine that can be found in plants, animals and microorganism. The metabolic pathway of melatonin is different in various organisms, and biosynthetic endogenous melatonin acts as a molecular signal and antioxidant protection against external stress. Microbial synthesis pathways of melatonin are similar to those of animals but different from those of plants. At present, the method of using microorganism fermentation to produce melatonin is gradually prevailing, and exploring the biosynthetic pathway of melatonin to modify microorganism is becoming the mainstream, which has more advantages than traditional chemical synthesis. Here, we review recent advances in the synthesis, optimization of melatonin pathway. l-tryptophan is one of the two crucial precursors for the synthesis of melatonin, which can be produced through a four-step reaction. Enzymes involved in melatonin synthesis have low specificity and catalytic efficiency. Site-directed mutation, directed evolution or promotion of cofactor synthesis can enhance enzyme activity and increase the metabolic flow to promote microbial melatonin production. On the whole, the status and bottleneck of melatonin biosynthesis can be improved to a higher level, providing an effective reference for future microbial modification.