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An Overview of 7α- and 7β-Hydroxysteroid Dehydrogenases: Structure, Specificity and Practical Application

Journal

PROTEIN AND PEPTIDE LETTERS
Volume 28, Issue 11, Pages 1206-1219

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/0929866528666210816114032

Keywords

7 alpha-hydroxysteroid dehydrogenase; 7 beta-hydroxysteroid dehydrogenase; short-chain dehydrogenase/reductase; substrate specificity; coenzyme specificity; stereoselectivity; protein engineering

Funding

  1. School-level Research Program of Chongqing University of Education [KY201710B]
  2. Chongqing Research Program of Basic Research and Frontier [cstc2018jcyjAX0811]
  3. Advanced Programs of Post-doctor of Chongqing [2017LY39]
  4. Youth Project of Science and Technology Research Program of Chongqing Education Commission of China [KJQN201901606]
  5. Chongqing Professional Talents Plan for Innovation and Entrepreneurship Demonstration Team [CQYC201903258]
  6. Science and Technology Research Program of Chongqing Municipal Education Commission [KJZD-K202001603]

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This article summarizes the structural characteristics, specificities, biochemical properties, and applications of 7 alpha-hydroxysteroid dehydrogenase and 7 beta-hydroxysteroid dehydrogenase. Emphasis is placed on obtaining novel enzymes that are thermally stable and active under specific conditions.
7 alpha-Hydroxysteroid dehydrogenase and 7 beta-hydroxysteroid dehydrogenase are key enzymes involved in bile acid metabolism. They catalyze the epimerization of a hydroxyl group through 7-keto bile acid intermediates. Basic research of the two enzymes has focused on exploring new enzymes and the structure-function relationship. The application research focused on the in vitro biosynthesis of bile acid drugs and the exploration and improvement of their catalytic ability based on molecular engineering. This article summarized the primary and advanced structural characteristics, specificities, biochemical properties, and applications of the two enzymes. The emphasis is also given to obtaining novel 7 alpha-hydroxysteroid dehydrogenase and 7 beta-hydroxysteroid dehydrogenase that are thermally stable and active in the presence of organic solvents, high substrate concentration, and extreme pH values. To achieve these goals, enzyme redesigning based on protein engineering and genomics may be the most useful approaches.

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