H2-driven biocatalysis for flavin-dependent ene-reduction in a continuous closed-loop flow system utilizing H2 from water electrolysis

Communications Chemistry, vol. 7, pp. 200

Abstract

Abstract Despite the increasing demand for efficient and sustainable chemical processes, the development of scalable systems using biocatalysis for fine chemical production remains a significant challenge. We have developed a scalable flow system using immobilized enzymes to facilitate flavin-dependent biocatalysis, targeting as a proof-of-concept asymmetric alkene reduction. The system integrates a flavin-dependent Old Yellow Enzyme (OYE) and a soluble hydrogenase to enable H2-driven regeneration of the OYE cofactor FMNH2. Molecular hydrogen was produced by water electrolysis using a proton exchange membrane (PEM) electrolyzer and introduced into the flow system via a designed gas membrane addition module at a high diffusion rate. The flow system shows remarkable stability and reusability, consistently achieving >99% conversion of ketoisophorone to levodione. It also demonstrates versatility and selectivity in reducing various cyclic enones and can be extended to further flavin-based biocatalytic approaches and gas-dependent reactions. This electro-driven continuous flow system, therefore, has significant potential for advancing sustainable processes in fine chemical synthesis.

Authors 7

1. Guiyeoul Lim Aachen Institute of Applied Microbiology - iAMB

   RWTH Aachen University

   Affiliation as printed

   Institute of Applied Microbiology-iAMB RWTH Aachen University, Aachen, Germany

2. Allison E. Wolder

   Delft University of Technology

   Affiliation as printed

   Biocatalysis Section, Department Biotechnology, Delft University of Technology, Delft, The Netherlands

3. Paul R. F. Cordero Aachen Institute of Applied Microbiology - iAMB

   RWTH Aachen University

   Affiliation as printed

   Institute of Applied Microbiology-iAMB RWTH Aachen University, Aachen, Germany

4. Dörte Rother Aachen Institute of Applied Microbiology - iAMB

   Forschungszentrum Jülich · RWTH Aachen University

   Affiliation as printed

   Institute for Bio-and Geosciences 1: Biotechnology Forschungzentrum Jülich GmbH, Jülich, Germany

   Institute of Applied Microbiology-iAMB RWTH Aachen University, Aachen, Germany

5. Florian F. Mulks Aachen Institute of Organic Chemistry-iOC

   RWTH Aachen University

   Affiliation as printed

   Institute of Organic Chemistry-iOC RWTH Aachen University, Aachen, Germany

6. Caroline Emilie Paul

   Delft University of Technology

   Affiliation as printed

   Biocatalysis Section, Department Biotechnology, Delft University of Technology, Delft, The Netherlands

7. Lars Lauterbach corresponding Aachen Institute of Applied Microbiology - iAMB

   RWTH Aachen University

   Affiliation as printed

   Institute of Applied Microbiology-iAMB RWTH Aachen University, Aachen, Germany. lars.lauterbach@iamb.rwth-aachen.de