Fernando López Gallego

Spatial compartmentalization of chemoenzymatic cascades with heterogeneous (bio)catalysts

The combination of chemical and biological catalysts allows access to synthetic pathways that would otherwise be inaccessible when using either catalyst type alone. However, most chemo-enzymatic pathways have been constrained by compatibility issues. (1) Catalyst compartmentalization proves to be an effective strategy to address these challenges. In this study, we showcase the immobilization of a gold catalyst and the versatile ketoreductase from Lactobacillus kefir (2, 3) for a model three-step chemo-enzymatic cascade, converting 4-pentynoic acid into 4-(R)-hydroxy valeric acid with high enantioselectivity. To achieve this, we employ two packed-bed reactors that physically separate a chemoenzymatic cycloisomerization/hydrolysis step from the self-sufficient biocatalytic asymmetric reduction (Figure 1). Consequently, the chemo-enzymatic system, operating continuously at pH 3.8, maintains a consistent space-time yield (STY) of 0.47 g L-1 h-1 over 24 hours, underscoring the remarkable operational stability of the catalysts. Overall, our results underscore the significance of spatially orchestrating catalysts to develop efficient hybrid chemo-enzymatic cascades.

Figure 1. Performance of the optimized hybrid chemo-enzymatic flow-system formed by two telescoped PBRs loading a gold-catalyst (BMEAu@AG-DEAE; cyan), an immobilized lipase (N435; grey), and a self-sufficient immobilized KRED (ssLkKRED@AG-Co2+/E/PAH; tourquise) for the continuous transformation of pentynoic acid into 4-hydroxyvaleric acid.

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[1] R. Ye, J. Zhao, B.B. Wickemeyer, F.D Toste and G.A. Somorjai, Nat. Catal. 2018 1, 318-325
[2] A.I Benítez-Mateos, E. San Sebastian, N. Ríos-Lombardía, F. Morís, J., González-Sabín, and F. López-Gallego, Chem. Eur. J. 2018, 223, 16843-16852
[3] D. Andrés-Sanz, A. Maiz-Iginitz, J.M. Bolivar, A. Orrego, H. Sardon, F. López-Gallego. ChemRxiv (Preprint) 2024. doi:10.26434/chemrxiv-2024-ws15r.
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OP3_Fernando López Gallego.pdf

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Mon. April 15 | 11:00 – 10:20 hrs – Spatial compartmentalization of chemoenzymatic cascades with heterogeneous (bio)catalysts