Coding

Part:BBa_K5378001:Design

Designed by: pan zhao   Group: iGEM24_SMU-GDMU-CHINA   (2024-09-24)


Trp hydroxylase-1 (TPH1)


Assembly Compatibility:
  • 10
    COMPATIBLE WITH RFC[10]
  • 12
    COMPATIBLE WITH RFC[12]
  • 21
    COMPATIBLE WITH RFC[21]
  • 23
    COMPATIBLE WITH RFC[23]
  • 25
    COMPATIBLE WITH RFC[25]
  • 1000
    COMPATIBLE WITH RFC[1000]


Design Notes

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.



Source

Homo sapiens (human)

References

[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.

[2] Watts, S.W., Morrison, S.F., Davis, R.P., and Barman, S.M. (2012). Sero tonin and blood pressure regulation. Pharmacol. Rev. 64, 359–388. https://doi.org/10.1124/pr.111.004697.

[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.