Team:Shanghai HS United/Description
Description
Background
As a primary part of lactose, galactose is found in most galactose products and many baby formulas. But it is dangerous for galactosemia patients to eat galactose products. Galactosemia is an autosomal recessive disorder disease leading to abnormal in using galactose to produce energy. The patients have galactose 1-phosphate uridyltransferase (GALT) deficiency. There are three kinds of this disease: Type 1 galactosemia occurs in 1 out of every 6000-10000 babies, Type 2 galactosemia is less common than type 1 and occurs in 1 out of every 100,000 babies, Type 3 and Duarte variant galactosemia are very rare. Long-term outcome for older patients with galactosemia remains problematic although neonatal hepatotoxic syndrome is prevented by newborn screening and galactose restriction.
Inspiration
After having several seminars with experts in this area, we learned that there are three therapies for this disease. The first one is to decrease or cease the intake quantity of galactose products. The second one is to increase the intake quantity of relative enzymes: uridyltransferase, galactokinase, and galactose epimerase. And the last one is to cure the complications when those patients grow up. There are countless microorganisms in human intestines since gut flora is important for health. In detail, the gut flora interacts with carbohydrates and converts them into short-chain fatty acid. About 95% of the short-chain fatty acids in our bodies butyric acid is the most beneficial one.
Based on the information presented above, we came up with the plan using engineering probiotics to degrade and digest the galactose in galactosemia patients.
Our goal is to engineer plasmid No. 4 that has a butyric acid synthesis pathway along with a lac-Y gene that helps the probiotic to prioritize the ingestion of galactose. Plasmid No. 4 has a function of enabling the probiotic to change galactose in our intestine to butyric acid. To obtain plasmid No. 4, we need to combine Plasmid No. 1 and Plasmid No. 2. Plasmid No. 1 is constructed with a pMTL83151 carrier, butyrate synthesis path gene，and J23100 promoter. Plasmid No. 2 uses P-15A as its carrier with lacY gene and J23200 promoter connected. That’s to say we can transform the plasmid into probiotics, which results a better ambient in the intestine making the lactose easier to be absorbed. And our products can be made as lactic acid beverage, lactic acid bacteria powder or lactobacillus capsules.
Citations:
Morrison, D. J., & Preston, T. (2016). Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes, 7(3), 189-200. doi:10.1080/19490976.2015.1134082
Vergara, D. M. (2017). Ácidos grasos de cadena corta (ácido butírico) y patologías intestinales. Nutrición Hospitalaria, 34(4). doi:10.20960/nh.1573
Coelho, A. I., Rubio-Gozalbo, M. E., Vicente, J. B., & Rivera, I. (2017). Sweet and sour: An update on classic galactosemia. Journal of Inherited Metabolic Disease, 40(3), 325-342. doi:10.1007/s10545-017-0029-3
Welling, L., Bernstein, L. E., Berry, G. T., Burlina, A. B., Eyskens, F., Gautschi, M., Bosch, A. M. (2016). International clinical guideline for the management of classical galactosemia: Diagnosis, treatment, and follow-up. Journal of Inherited Metabolic Disease, 40(2), 171-176.doi: 10.1007/s10545-016-9990-5
Karadag, N., Zenciroglu, A., Eminoglu, F., Dilli, D., Karagol, B., Kundak, A., Okumus, N. (2013). Literature Review and Outcome of Classic Galactosemia Diagnosed in the Neonatal Period. Clinical Laboratory, 59(09 10/2013). doi: 10.7754/clin.lab.2013.121235
Wechat: Search "iGEM GalAcid团队" in WeChat