Generator

Part:BBa_K1598004

Designed by: Marta Napiorkowska   Group: iGEM15_UCL   (2015-08-27)

RBS-GAD-6xHis-Terminator

This part consists of B0034 RBS, human glutamate decarboxylase (GAD) gene with C-terminal His tag, and B0015 terminator.

Usage and Biology

GABA is synthesized from glutamate in the reaction catalyzed by L-glutamic acid decarboxylase (GAD) catalyzes decarboxylation of glutamate to gamma-aminobutyric acid (GABA). We have created the device for overexpression of GAD and we suggest to investigate the therapeutic potential of administration of GABA-overexpressing probiotics to patients with decreased GABA levels.

GABA is the main inhibitory neurotransmitter in the brain and decreased GABA levels have been linked to depression and anxiety [1]. Several species of gut bacteria have been shown to produce GABA [2] and metabolomics analysis has shown that the gut luminal GABA levels in ex-germfree mice are considerably higher than those observed in germfree mice [3] . The role of microbiota-derived GABA in gut-brain signalling can be supported by the presence of GABA receptors in gut epithelial cells [4].

The positive effects of GABA-producing species in the gut on the emotional behaviour of the host have been previously documented. In one study, administration of milk enriched in GABA-producing Lactobacillus brevis FPA 3709 had antidepressant effect on mice [5]. Another study has shown that ingestion of Lactobacillus rhamnosus alters GABA mRNA expression in the host's brain and reduces the stress-induced and depression-related behaviour [6].


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
    INCOMPATIBLE WITH RFC[25]
    Illegal AgeI site found at 658
    Illegal AgeI site found at 718
  • 1000
    COMPATIBLE WITH RFC[1000]


References

[1] Kalueff, A. and Nutt, D. (2007). Role of GABA in anxiety and depression. Depression and Anxiety, 24(7), pp.495-517.

[2] Cryan, J. and Dinan, T. (2012). Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nature Reviews Neuroscience, 13(10), pp.701-712

[3] Matsumoto, M., Kibe, R., Ooga, T., Aiba, Y., Kurihara, S., Sawaki, E., Koga, Y. and Benno, Y. (2012). Impact of Intestinal Microbiota on Intestinal Luminal Metabolome. Sci. Rep., 2.

[4] Li, Y., Xiang, Y., Lu, W., Liu, C. and Li, J. (2012). A novel role of intestine epithelial GABAergic signaling in regulating intestinal fluid secretion. AJP: Gastrointestinal and Liver Physiology, 303(4), pp.G453-G460.

[5] Ko, C., Lin, H. and Tsai, G. (2013). Gamma-aminobutyric acid production in black soybean milk by Lactobacillus brevis FPA 3709 and the antidepressant effect of the fermented product on a forced swimming rat model. Process Biochemistry, 48(4), pp.559-568.

[6] Bravo, J., Forsythe, P., Chew, M., Escaravage, E., Savignac, H., Dinan, T., Bienenstock, J. and Cryan, J. (2011). Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences, 108(38), pp.16050-16055

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