H 2 -driven biocatalysis for flavin-dependent ene-reduction in a continuous closed-loop flow system utilizing H 2 from water electrolysis

• Published in: Communications chemistry 2024-09, Vol.7 (1), p.200
• Main Authors: Lim, Guiyeoul, Calabrese, Donato, Wolder, Allison, Cordero, Paul R F, Rother, Dörte, Mulks, Florian F, Paul, Caroline E, Lauterbach, Lars
• Format: Article
• Language: English
• ISSN: 2399-3669

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 H -driven regeneration of the OYE cofactor FMNH . 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.