Controlling the fatty acid hydroxylation regioselectivity of CYP152A1 (P450Bsb) by active site engineering
September 15-19, 2019
Regioselective hydroxylation on inactivated C-H bonds is among the dream reactions of organic chemists. Cytochrome P450 enzymes (CYPs) perform this reaction in general with high regio- and stereoselectivity (e.g. for steroids as substrates). Furthermore, enzyme engineering may allow to tune the regioselectivity of the enzyme. Regioselective in-chain hydroxylation of shorter or linear molecules (fatty acids), however, remains challenging even with this enzyme class, due to the high similarity of the substrate’s backbone carbons and their conformational flexibility. CYPs are well described for hydroxylating fatty acids selectively in the chemically more distinct a- or w-position. In contrast, selective in-chain hydroxylation of fatty acids lacks precedence. The peroxygenase CYP152A1 (P450Bsb) is a family member that displays fatty acid hydroxylation at both, the a- and b-position.
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Lucas Hammerer, Michael Frieß, Wolfgang Kroutil, Jeyson Cerne, Georg Steinkellner, Karl Gruber, Koenraad Vanhessche, Thomas Plocek, and Christoph K Winkler, "Controlling the fatty acid hydroxylation regioselectivity of CYP152A1 (P450Bsb) by active site engineering" in "Enzyme Engineering XXV", Huimin Zhao, University of Illinois at Urbana-Champaign, USA John Wong, Pfizer, USA Eds, ECI Symposium Series, (2019). https://dc.engconfintl.org/enzyme_xxv/49