Integrated electro-biocatalysis for chemical production in flow system

Introduction: Conventional batch reactions are commonly used in chemical synthesis but often fall short in terms of efficiency, scalability, and sustainability. Continuous flow systems offer a promising alternative by addressing these limitations, and incorporating electricity can further enhance process control and support sustainable chemical transformations1,2. Nonetheless, the potential of electro-biocatalytic flow systems remains underexplored.

Aim: Our aim was to evaluate H2-driven flavin-mediated reduction of cyclic enones in continuous flow setup for sustainable production of fine chemicals using electricity.

Method: This study utilized TsOYE for ene reduction and soluble hydrogenase (SH) for H2-driven recycling of FMNH2. H2 was supplied from water electrolysis by a PEM electrolyzer and fed into the flow system through gas-permeable membrane tubing inside a gas addition module. SH was immobilized on Strep-Tactin resin and TsOYE on EziG beads (SH-Tactin, TsOYE-EziG), both packed in a column integrated into the flow system.

Result: We demonstrated electro-driven asymmetric reduction of ketoisophorone to levodione in the flow setup. Subsequently, the setup was used to evaluate the reusability of the immobilized enzymes, where it maintained product formation of >99 % even after seven cycles. Finally, we demonstrated scalability of the system by increasing the flow reaction volume, with TTN of SH-Tactin and TsOYE-EziG reaching 3.2 x 105 and 2.6 x 104, respectively3.

Conclusion: In this study, we established a biocatalytic continuous-flow system using electrical energy to produce fine chemicals. Apart from integrating a PEM electrolyzer and highly gas-permeable tubing, this study also introduced Strep-Tactin resin and highlighted EziG beads as stable enzyme carriers suitable for applications in a scalable continuous-flow setup. Overall, we made advancements in continuous flow biocatalysis by incorporating H2 from water electrolysis into the flow system to fuel flavin-dependent reactions.

Reference:

Klos, N., … Lim, G., …, Lauterbach,L., Jupke, A., Leitner, W., Blank, L. M., Klankermayer, J., & Rother, D. (2024). JACS Au Article ASAPAl‐Shameri, A., Petrich, M.‑C., junge Puring, K., Apfel, U.‑P., Nestl, B. M., & Lauterbach, L.(2020). Angew. Chemie. 56(67), 9667–9670.Lim, G., Calabrese, D., Wolder, A., Cordero, P. R. F., Rother, D., Mulks, F. F., Paul, C. E., & Lauterbach, L. (2024). Commun. Chem. 7:1, 7(1), 1–7.