[Zurück]

F. Rudroff, M.D. Mihovilovic:
"Development of an Enzymatic Toolbox for RedOx Cascade Reactions From Asymmetric Functional Group Transformations to Complex Chiral Biocatalysis";
Vortrag: MECP14 Multienzyme catalyzed processes, Madrid, Spanien; 07.04.2014 - 10.04.2014; in: "MECP 14 Multienzyme catalyzed processes", (2014), S. 1 - 95.

We present a `general concept´ study by exploiting the manifoldness of enzymes and their different catalytic activities for the introduction of multi-enzymatic redox reactions in vivo.
The design of our artificial biosynthetic pathway composed of naturally non-related enzymes is based on a classical `retrosynthetic´ approach. This technique is used in the strategic planning of organic syntheses by transforming a target molecule into simpler precursors whereas molecular complexity is reduced by manipulation of functional groups. In this particular case, different redox enzyme classes are used as tools for such functional group transformations to design new non-natural enzymatic cascades.
Specifically, a three to four step artificial metabolic `mini-pathway´ composed of an alcohol dehydrogenase, for the oxidation of an allylic secondary cyclic alcohol to the corresponding α, β unsaturated ketone, an enoate reductase for the subsequent reduction of the double bond concluded by an Baeyer-Villiger monooxygenase for the formation of the corresponding lactone will be presented in this study. This particular sequence was realized as a proof-of-concept study to demonstrate the principal feasibility and to determine and resolve limiting aspects. Additionally, we will demonstrate the variability of this approach by the selection of various substrates to depict important aspects of biocatalytic reactions such as achiral transformations, desymmetrizations, and kinetic resolutions.

http://publik.tuwien.ac.at/files/PubDat_236689.pdf