Part:BBa_K5378088:Sequence, Features, and Subparts
Designed by: pan zhao Group: iGEM24_SMU-GDMU-CHINA (2024-09-25)
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Usage and Biology
A small amount of Trp is catalyzed to 5-HTP by TPH (Figure).Aromatic L-amino acid decarboxylase interacts
with the cofactor pyridoxal-5’-phosphate to convert 5-HTP to 5-HT. 5-HT is a monoamine neurotransmitter in
the human central nervous sys tem and is also known as serotonin because it can cause vascular smooth muscle
contraction when present in the blood. The synthesis of 5-HT takes place in both the gut and
brain.Peripheral 5-HT is primarily synthesized by TPH1 in the enterochromaffin cells. 5-HT is subsequently
stored in platelets and contributes to various physiological functions, including the regulation of
vasocontraction and proliferation of vascular smooth muscle cells.
We learned that 5-HT can be further converted to melatonin, which further regulates the sleep-wake cycle by
consulting the literature.Furthermore, 5-HT in the gut has been reported to be involved in the production of
melatonin.
Functional Verification
After being metabolized by gut bacteria, aromatic amino acids from food can produce monoamine false
neurotransmitters, such as phenylalanine being metabolized into phenylethylamine, and tyrosine into
tyramine. Tryptophan, through different metabolic pathways, can be converted into kynurenine, serotonin, and
indole[7].
Patients who develop liver failure can not digest those aromatic amino acids properly, and this can lead to
false neuro-transmitters accumulation, causing neuro system symptoms.
We designed a plasmid that can be transformed into EcN to express tryptophan hydroxylase 1 (TPH1), enabling
the conversion of tryptophan (Trp) into serotonin (5-HT) and reducing excess aromatic amino acids. Since
serotonin synthesized in the gut cannot cross the blood-brain barrier (BBB) or affect central nervous system
function, there is no concern about adverse effects on the central nervous system.
Reference
[1]Daubert, E.A., and Condron, B.G. (2010). Serotonin: a regulator of neuronal morphology and circuitry.
Trends Neurosci. 33, 424–434. https://doi.org/10.1016/j.tins.2010.05.005.
[3]Chen,C.Q., Fichna, J., Bashashati, M., Li, Y.Y., and Storr, M. (2011). Dis tribution, function and
physiological role of melatonin in the lower gut. World J. Gastroenterol. 17, 3888–3898.
https://doi.org/10.3748/wjg. v17.i34.3888.
[4]Xue C, Li G, Zheng Q, Gu X, Shi Q, Su Y, Chu Q, Yuan X, Bao Z, Lu J, Li L. Tryptophan metabolism in health
and disease. Cell Metab. 2023 Aug 8;35(8):1304-1326. doi: 10.1016/j.cmet.2023.06.004. Epub 2023 Jun 22.
PMID: 37352864.
