Team:HUST-China/Project

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            <p>Hypertension is sometimes called "<strong>silent killer</strong>", for you don't have any symptoms when actually your blood pressure is far beyond the healthy level, and for it has been identified as a risk factor for coronary artery disease (CAD) and Chronic renal failure (CRF). Although it causes grave concern worldwide for its notoriety, there are not many therapeutic methods to hypertension besides a wide selection among various antihypertensive drugs. However, this comes along with heavy financial burden to the developing countries or underdeveloped countries. In addition, almost all these drugs have side effects to liver and renal.<br>
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Suppose there is a group of friendly engineering bacteria in the human intestine and they can produce short-chain fatty acids (SCFA) periodically and naturally to help maintain the blood pressure in safe level. Will it be a novel method to treat Hypertension?<br>
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<strong>SCFA</strong>, especially acetate and propionate, has been proved to induce vasodilatation and ensuing hypotensive response via receptors in smooth muscle cells of vessels. This year, iGEM-HUST have found a metabolic pathway in Escherichia coli (E.coil) that converts succinate to propionate through Wood-Werkman reaction. An operon consisting four genes encodes enzymes in this pathway. By combining bio-oscillator and key gene together, we want to make E. Coli release propionate periodically in patients’ intestine periodically. Once the E.coli is delivered into human body as probiotics, the propionate can be taken by the circulatory system and act with the receptors. However, all the works we have done at present were processed in vitro since we are not sure about the effective concentration for therapy in different patients. And what we are considering is how to prolong the period of propionate and correspond with the peak valley of blood pressure.
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            <strong class="lead">A four gene operon Figure1 in Escherichia coli genome which include sbm(scpA) ygfG ygfH ygfD, is significant in the metabolic pathway that converts succinate to propionate through Wood-Werkman reaction. </strong>
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<blockquote>Sbm encodes methylmalonyl-CoA epimerase which catalyzes the reversible reaction of succinyl-CoA and methylmalonyl-CoA, the first step in the propionate synthetic pathway. YgfG encoding by the third gene in the operon, catalyzes the decarboxylation of methylmalonyl-CoA to propionyl-CoA. And YgfH catalyzes a CoA transferase reaction from propionyl-CoA to succinyl, generating propionate. Yet the function of YgfD is not as clear as the remaining three. According to Toomas Haller, the protein encoded by the second gene, YgfD, contains a consensus binding sequence for ATP. They thought it might be a succinate (or propionate) CoA ligase, or a novel (biotin-independent) propionyl-CoA carboxylase. So far, what we confirm is its indispensable importance in the pathway.</blockquote>
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            <li>Jennifer L. Pluznick, Ryan J. Protzko, Haykanush Gevorgyan, Zita Peterlin, Arnold Sipos, Jinah Han,ect. Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. PNAS Early Edition, Approved January 4, 2013.</li>
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            <li>RIVERS SINGLETON, JR. Heterotrophic CO2-Fixation, Mentors, and Students: The Wood-Werkman ReactionS. Journal of the History of Biology 30: 91–120, 1997</li>
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            <li>Anne Thierry, Stéphanie-Marie Deutsch, Hélène Falentin, Marion Dalmasso, Fabien J. Cousin, Gwenaël Jan. New insights into physiology and metabolism of Propionibacterium freudenreichii. International Journal of Food Microbiology 149 (2011) 19 – 27</li>
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            <li>Toomas Haller, Thomas Buckel, Ja ´nos Re´tey, and John A. Gerlt. Discovering New Enzymes and Metabolic Pathways: Conversion of Succinate to Propionate by Escherichia coli. Biochemistry2000, 39, 4622-4629</li>
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