serotonin

Serotonin is a tryptophan-derived neurotransmitter and molecule naturally present in both animals and plants [146, 338]. It is biosynthesized through two primary routes: the decarboxylation of 5-hydroxytryptophan (5HTP) or the hydroxylation of tryptamine [338]. Serotonin exhibits biological activities, including free radical scavenging and antioxidant properties [338]. It also serves as a precursor for other biomolecules, such as melatonin, while its indole scaffold is recognized by various therapeutic targets, including 5-hydroxytryptamine and cannabinoid receptors [338].

A common metabolic engineering strategy for serotonin production involves the heterologous expression of an engineered aromatic amino acid hydroxylase to convert tryptophan into 5HTP, coupled with an artificial regeneration system for the essential pterin cofactor using enzymes such as PCD and DHPR [338]. The resulting 5HTP is subsequently converted into serotonin by tryptophan decarboxylase (TDC), such as the enzyme from Catharanthus roseus [338]. However, undesired side reactions can limit production efficiency because TDC exhibits a strong preference for tryptophan, resulting in the accumulation of tryptamine rather than the desired product. To address this limitation, metabolic engineering strategies include protein engineering of the hydroxylase to enhance its catalytic activity and the implementation of two-stage fermentation processes that separate 5HTP production from its subsequent conversion into serotonin [338].