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Project 8 Dr. Wolfgang Hüttel

Stereoselective β–hydroxylation of carboxylic acids with α–ketoglutarate dependent hydroxylases

Fe(II)- and α-ketoglutarate dependent non-heme dioxygenases  are a large group of oxidoreductases catalyzing CH-activation reactions, mainly hydroxylations. They are highly regio- and stereoselective, easy to handle, use readily available cofactors (co-substrates) and therefore have a great potential as biocatalysts for the production of rare chiral building blocks.
In this project the reaction of the of γ-Butyrobetaine hydroxylase (BBH) will be utilized for the stereoselective β-hydroxylation of carboxylic acids. As the trimethylammonio group in the native product, L-carnitine, is unsuitable as chemical building block, the project will focus on the acceptance of nonnatural substrates by wild-type enzymes and engineered variants. Besides substrate screening of wildtype enzymes, optimized variants shall be designed on the basis of published and new crystal structures (cooperation with Oliver Einsle), electron spin resonance (ESR) analysis (cooperation with Erick Scheicher) and molecular docking (cooperation with Stefan Günther)






Dr. Wolfgang Hüttel

Institute of Pharmaceutical Sciences

Pharmaceutical and Medicinal Chemistry

Albertstr. 25

79104 Freiburg

Phone: +49 (0) 761 203-4895

Fax:+49 (0) 761 203-6351

email: wolfgang.huettel@pharmazie.uni-freiburg.de



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