Difference between revisions of "Team:SDSZ-China"

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{{SDSZ-China}}
 
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                    <li><a href="/Team:SDSZ-China">Home</a></li>
 
                    <li><a href="/Team:SDSZ-China/Project">Project</a></li>
 
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                    <li><a href="/Team:SDSZ-China/Safety">Safety</a></li>
 
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                    <li><a href="/Team:SDSZ-China/Team">Team</a></li>
 
                    <li><a href="#">By SDSZ</a></li>
 
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                    <li><a href="#Background">Background</a></li>
 
                    <li><a href="#Purpose">Purpose</a></li>
 
                    <li><a href="#Overview">Overview of the project</a></li>
 
                    <li><a href="#Goal">Our goal</a></li>
 
 
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                    <h2 id='Background'>Background</h2>
 
                    <p>Bear bile, one of the most famous animal drugs in Traditional Chinese Medicine (TCM), has been
 
                        recorded in ancient Chinese medicine book as a significant method to treat hepatic and biliary
 
                        disorders. UDCA, the effective ingredient of bear bile.Aside from the traditional use of bear
 
                        bile in Chinese medicine, UDCA(ursodeoxycholic acid), the effective ingredient of bear bile
 
                        acid, has a much larger pharmaceutical application. As well as the usage of UDCA in dissolving
 
                        gallstone, its efficacy in primary biliary cirrhosis and primary sclerosing cholangitis (PSC) as
 
                        an adjunct to medical therapy has been well established. Newer indications include its use in
 
                        the management of chronic hepatitis, cirrhosis, post liver transplant rejection,
 
                        graft-versus-host disease and acute viral hepatitis, where it not only relieves symptoms of
 
                        cholestasis but also arrests ongoing hepatocyte necrosis. However, the increasing demand for
 
                        bear bile has caused bears to be in an endangered state: bear poaching and illegal animal trade
 
                        have greatly dwindled the number of the wild Asiatic black bear. Apart from that, bear bile
 
                        farming industry in Asia extracts bile through “milking” from the bears, which is operated
 
                        through surgically implanting a permanent catheter in the animal's gallbladder to obtain the
 
                        drips. It is unquestionable that the bear bile farming process will lead to both physical and
 
                        psychological damage in bears. </p>
 
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                    <h2 id='Purpose'>Purpose</h2>
 
                    <p>To find substitute or alternative for bear bile farming, our team will be working on the
 
                        biological synthesis of the main effective component of this important medicine,
 
                        UDCA(Ursodeoxycholic Acid). This biological approach will not only be more efficient but also be
 
                        cheaper than the original chemical approach, which is widely used in the current UDCA synthesis
 
                        industry. </p>
 
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                    <h2 id='Overview'>Overview of the project</h2>
 
                    <p>We found that it is possible to convert the main component of poultry bile, CDCA(Chenodeoxycholic
 
                        Acid), into UDCA, by employing two enzyme-catalyzed the reactions. First, two enzymes was
 
                        employed to manage the transformation of CDCA to 7oxo-LCA. In the present of
 
                        7a-HSD(7alpha-hydroxysteroid dehydrogenase), CDCA is transformed in to 7oxo-LCA by loosing a
 
                        pair of hydrogen(2H+ and 2e-), the pair of hydrogen is added to NAD+, the cofactor and the
 
                        acceptor. The NAD+ is transformed into NADH during the reaction. To regenerate the NAD+ and
 
                        recycle the reaction, to , the LDH(Lactate dehydrogenase) works on pyruvate and take the pair of
 
                        hydrogen from NADH and transform the pyruvate to lactate and NADH to NAD+.</p>
 
                    <p>In the second step, the 7oxo-LCA is transformed to UDCA by 7β-HSDH(7beta-hydroxysteroid
 
                        dehydrogenase)and GDH(glutamate dehydrogenase).The 7β-HSDH works on 7oxo-LCA and take a pair of
 
                        hydrogen from NADPH(the cofactor for the second step)and add it to 7oxo-LCA and form a beta
 
                        position 7-hydroxyl group, which is our target product UDCA. The GDH works on glucose and take a
 
                        pair of hydrogen from it and add it to the NADP+, to form NADPH to manage the regeneration of
 
                        cofactor NADPH for the second step.</p>
 
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                    <h2 id='Goal'>Our goal</h2>
 
                    <p>Our mission is to expression of the four enzymes 7α-HSDH (from ecoli DH5a), 7β-HSDH (from
 
                        Ruminococcus Torques), GDH (from Bacillus subtilis), and LDH from (Lactobacillus delbruechii
 
                        subsp. Bulgaricus)and test their activities. By adding the CBD( cellulose binding
 
                        domain)sequnence to the plasmid we construct, we manage to bind our enzyme on gauze. This
 
                        specific design excels in 3 specific ways: first, by controlling the presence of the gauze in
 
                        the solution, we can control the process of the reaction. Second, when the target enzyme is
 
                        bound to cellulose we manage to purify the protein we express. Third, the enzyme binding gauze
 
                        is employed to a machine including the reaction efficiency measuring system and the enzyme
 
                        addition controlling system .</p>
 
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Revision as of 12:56, 1 November 2017