Coding

Part:BBa_K1598001

Designed by: Marta Napiorkowska   Group: iGEM15_UCL   (2015-06-18)

TPH1 (Tryptophan hydroxylase 1)

With the aim to address serotonin deficiency and dysregulation of gut-brain communication in patients with mental health disorders and we have developed and characterized the biobrick that overexpresses human tryptophan hydroxylase for 5-HTP production. This is the intermediate construct consisting of the human TPH1 gene alone. This construct was used in the assembly of BBa_K1598002.

Usage and Biology

Serotonin is an essential metabolite, key neurotransmitter in mood regulation and a target of vast majority of antidepressant drugs. The majority of serotonin in the body is produced by enterochromaffin cells located in the gut [1]. Metabolomics study has revealed that serotonin levels in blood plasma are 2.8 fold higher in conventional as opposed to germ-free mice [2], suggesting that the interactions between host and gut microflora play crucial role in regulating the production of serotonin and functioning of serotonergic system. The rate-limiting step of synthesis of serotonin is catalyzed by Tryptophan hydroxylase, TPH, which converts tryptophan, an essential amino acid, into 5-hydroxytryptophan (5-HTP) [3]. It was shown that germ-free mice exhibit decreased expression of tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, in enterochromaffin cells and decreased level of serotonin in the colon and the blood and that both recolonization of the gut and supplementation with 5-HTP, a product of TPH, restore the serotonin levels [4].

Sequence and Features

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]


Functional Parameters

You can access the characterization data for this part cloned into Lac inducible expression casette here

References

[1] Manocha, M. and Khan, W. Serotonin and GI Disorders: An Update on Clinical and Experimental Studies. Clinical and Translational Gastroenterology, 2012, 3(4), p.e13
[2] Wikoff, W., Anfora, A., Liu, J., Schultz, P., Lesley, S., Peters, E. and Siuzdak, G. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proceedings of the National Academy of Sciences, 2009, 106(10), pp.3698-3703
[3] O’Mahony, S., Clarke, G., Borre, Y., Dinan, T. and Cryan, J. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behavioural Brain Research, 2015, 277, pp.32-48.
[4] Yano, J., Yu, K., Donaldson, G., Shastri, G., Ann, P., Ma, L., Nagler, C., Ismagilov, R., Mazmanian, S. and Hsiao, E. Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis. Cell, 2015, 161(2), pp.264-276.

[edit]
Categories
//cds/biosynthesis
//cds/enzyme
Parameters
None