{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T17:49:17Z","timestamp":1773683357214,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,2,2]],"date-time":"2015-02-02T00:00:00Z","timestamp":1422835200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Federal Ministry of Education and Research, Germany","award":["0315878"],"award-info":[{"award-number":["0315878"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Progress"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:p>Ursodeoxycholic acid (UDCA) is a bile acid which is used as pharmaceutical for the treatment of several diseases, such as cholesterol gallstones, primary sclerosing cholangitis or primary biliary cirrhosis. A potential chemoenzymatic synthesis route of UDCA comprises the two\u2010step reduction of dehydrocholic acid to 12\u2010keto\u2010ursodeoxycholic acid (12\u2010keto\u2010UDCA), which can be conducted in a multienzymatic one\u2010pot process using 3\u03b1\u2010hydroxysteroid dehydrogenase (3\u03b1\u2010HSDH), 7\u03b2\u2010hydroxysteroid dehydrogenase (7\u03b2\u2010HSDH), and glucose dehydrogenase (GDH) with glucose as cosubstrate for the regeneration of cofactor. Here, we present a dynamic mechanistic model of this one\u2010pot reduction which involves three enzymes, four different bile acids, and two different cofactors, each with different oxidation states. In addition, every enzyme faces two competing substrates, whereas each bile acid and cofactor is formed or converted by two different enzymes. First, the kinetic mechanisms of both HSDH were identified to follow an ordered bi\u2013bi mechanism with EBQ\u2010type uncompetitive substrate inhibition. Rate equations were then derived for this mechanism and for mechanisms describing competing substrates. After the estimation of the model parameters of each enzyme independently by progress curve analyses, the full process model of a simple batch\u2010process was established by coupling rate equations and mass balances. Validation experiments of the one\u2010pot multienzymatic batch process revealed high prediction accuracy of the process model and a model analysis offered important insight to the identification of optimum reaction conditions. \u00a9 2015 American Institute of Chemical Engineers <jats:italic>Biotechnol. Prog.<\/jats:italic>, 31:375\u2013386, 2015<\/jats:p>","DOI":"10.1002\/btpr.2036","type":"journal-article","created":{"date-parts":[[2015,1,13]],"date-time":"2015-01-13T05:36:10Z","timestamp":1421127370000},"page":"375-386","source":"Crossref","is-referenced-by-count":8,"title":["Dynamic mechanistic modeling of the multienzymatic one\u2010pot reduction of dehydrocholic acid to 12\u2010keto ursodeoxycholic acid with competing substrates and cofactors"],"prefix":"10.1002","volume":"31","author":[{"given":"Boqiao","family":"Sun","sequence":"first","affiliation":[{"name":"Inst. of Biochemical Engineering, Dept. of Mechanical Engineering Technische Universit\u00e4t M\u00fcnchen Garching 85748 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Hartl","sequence":"additional","affiliation":[{"name":"Inst. of Biochemical Engineering, Dept. of Mechanical Engineering Technische Universit\u00e4t M\u00fcnchen Garching 85748 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