Scaling Up Is Not the Same but Bigger: Overcoming (Some) Limitations in Enzymatic Decarboxylations in Rotating Bed Reactors in Deep Eutectic Solvents

Deep eutectic solvents (DESs) can be designed to be enzyme-compatible and substrate solubilizers. Most biocatalytic reactions in DESs are conducted at small scale, and assessing how to scale up DES-based enzymatic reactions is necessary to assess their feasibility and associated challenges. This work studies the viability of using DESs with a phenolic acid decarboxylase (PAD) to synthesize 4-vinylguaiacol (4-VG) from ferulic acid. Upon PAD immobilization, the reaction is performed in a betaine–glycerol DES (1:2) with 20 vol % buffer in a rotating bed reactor (RBR) at the 120 mL scale. Full conversion of 300 mM ferulic acid (∼58 g/L) is achieved within 18 h at the 10 mL scale. However, challenges a substrate loadings are intended (1 M ferulic acid, ∼200 g/L) in the RBR at 120 mL, where ∼60% conversion is obtained, with a productivity of ∼10 g product/L/h. The formation of CO2 during the decarboxylation adds complexity at high substrate loadings, as part of the CO2 remains in the DESs and may change the physical–chemical properties. The produced 4-VG can be extracted with heptane (∼29% high-purity, one single extraction step). Overall, results demonstrate the feasibility of the DES/biocatalyst in RBRs for industrial applications, although they also reflect unexpected challenges (e.g., CO2 accumulation, low conversions). Research is needed to understand the pre-scale-up of DES-biocatalytic systems, as well as in the identification of biogenic alternatives for liquid–liquid separations.