Project Details
Projekt
Chiral alcohols from alkenes and water: Enzyme engineering, mechanistic insights & development of a broadly applicable synthetic platform
Subject Area
Biological and Biomimetic Chemistry
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 540930768
Enantioselective synthesis of chiral alcohols through asymmetric addition of water across alkenes is a highly sought-after transformation and a big challenge in catalysis. Here we propose a joint research project to develop, mechanistically understand and explore a biocatalytic “alkene hydratase” platform for sustainable synthesis of chiral alcohols using only alkenes and water as reactants. This is based on directed enzyme evolution of fatty acid hydratases to generate a large panel of hydratase variants that perform alkene hydration on a broad set of alkenes with high activity and selectivity. Fatty acid hydratases achieve highly enantioselective addition of water across unactivated alkenes through cooperative Brønsted acid/base catalysis. However, in their native form they are highly specific and, thus, limited to the use of the corresponding fatty acid as substrate. Therefore, one key aspect of this proposal are mechanistic studies to shed further light on the mechanism of fatty acid hydratases, which will i) provide insights into the role of a non-redox-active flavin cofactor, ii) guide process development and iii) simplify future rational enzyme engineering efforts of hydratases. The directed enzyme evolution as well as the mechanistic studies are accompanied by the design of a practical and broadly applicable “alkene hydratase” platform to enable multigram-scale synthesis of chiral alcohols from simple starting materials. Conducting this research project jointly is of importance as the design of the synthetic platform will influence and direct the enzyme evolution campaign. Furthermore, engineered hydratases will not only be studied as stand-alone catalyst in synthesis but will also be integrated in chemoenzymatic one-pot cascade processes to achieve overall reactions that are currently not possible otherwise.
DFG Programme
Research Grants
International Connection
Spain
Cooperation Partner
Dr. Marc Garcia-Borràs
