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Title: Enzyme Promiscuity in Serotonin Biosynthesis, From Bacteria to Plants and Humans
Authors: Gonçalves, Sara
Nunes-Costa, Daniela
Cardoso, Sandra Morais 
Empadinhas, Nuno 
Marugg, John David 
Keywords: aromatic amino acid decarboxylase; biosynthetic pathways; melatonin; serotonin; substrate promiscuity
Issue Date: 2022
Publisher: Frontiers
Project: LA/P/0058/2020 
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04539/2020/PT 
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP/04539/2020/PT 
info:eu-repo/grantAgreement/FCT/POR_CENTRO/SFRH/BD/117777/2016/PT/Functional and structural insights into the regulation of mycobacterial MGLP biosynthesis 
Serial title, monograph or event: Frontiers in Microbiology
Volume: 13
Abstract: Serotonin is a phylogenetically ancient compound found in animals, plants, and some bacteria. In eukaryotes, serotonin is synthesized from the aromatic amino acid tryptophan via the key enzymes aromatic amino acid hydroxylase (AAAH) and aromatic amino acid decarboxylase (AAAD). Serotonin is also an intermediate in the melatonin biosynthetic pathway and is involved in several vital functions. In humans, serotonin is produced in the gut and in the brain, is critical in the regulation of multiple body functions, and its depletion has been implicated in multiple neurological disorders including depression and Alzheimer's disease, as well as other peripheral conditions namely irritable bowel syndrome and fibromyalgia. The serotonin biosynthetic pathway is well described in eukaryotes, but very little is known about this pathway in bacteria. Evidence points to similar pathways since eukaryote-like AAAH and AAAD (and their genes) have been identified in multiple bacteria, even though serotonin production has not yet been detected in most species. Although data on bacterial tryptophan decarboxylase genes are very limited and no bacterial tryptophan hydroxylase genes have been identified to date, evidence suggests that serotonin production in bacteria might occur through different AAAH and AAAD. Substrate promiscuity in these enzymes has been previously reported and seems to be the key aspect in bacterial serotonin synthesis. Considering the human gut microbiota as a potential source of serotonin, further investigation on its biosynthetic pathways in microbes might lead to important discoveries, which may ultimately foster the development of new therapeutic strategies to treat serotonin depletion-related disorders in humans.
ISSN: 1664-302X
DOI: 10.3389/fmicb.2022.873555
Rights: openAccess
Appears in Collections:I&D CIBB - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais
IIIUC - Artigos em Revistas Internacionais

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