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Application L2506

Integration of Medium Engineering, Immobilization, and Rotating Bed Reactor for Intensifying Enzymatic Reduction of Halogenated Aryl Ketones

Shuling Zhang, Jiajing Yan, Quan Yuan, Yanjun Jiang, Lihui Wang, Yunting Liu

ACS Sustainable Chem. Eng., 2025, 13(50), pp. 21880–21889.

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Enzymatic reduction of halogenated aryl ketones (HAKs) is an important reaction for the synthesis of pharmaceutical-related enantiopure halohydrins, but its preparative application remains restricted due to low substrate solubility and poor mass transfer in aqueous media. Herein, a multiengineering approach involving medium optimization, enzyme immobilization, and a rotating bed reactor was applied for intensifying the enzymatic reduction of HAKs. A deep eutectic solvent (DES) composed of betaine, glucose, and water (Bet-Glc-H₂O) was demonstrated to be effective in improving enzymatic activity and stability, enabling efficient reduction of high-concentration HAKs (1.0 M, 85% conversion). In addition, enzyme immobilization was conducted using DES-modified resin supports, markedly enhancing the operational stability and reusability of the biocatalysts. Finally, a SpinChem rotating bed reactor (RBR) was implemented for further intensifying the enzymatic process, leading to dramatically shorter reaction times and increased overall productivity.

Keywords

ketoreductases, chiral halohydrins, deep eutectic solvents, bioprocess development, biocatalysis, enzyme immobilization

 

Schematic of the integrated approach combining a betaine–glucose–water deep eutectic solvent, immobilization on DES‑modified resin, and a SpinChem rotating bed reactor to intensify the enzymatic reduction of halogenated aryl ketones.

Application L2506

 

Highlights:

  • Deep eutectic solvent boosts enzymatic performance: A DES system (Bet-Glc-H₂O) improved both enzymatic activity and stability, enabling efficient reduction of high-concentration halogenated aryl ketones at 1.0 M substrate loading with 85% conversion
  • DES-modified resin supports enhance reusability: Enzyme immobilization on DES-modified resin carriers markedly improved operational stability and biocatalyst reusability for repeated reaction cycles
  • SpinChem RBR dramatically accelerates the process: Implementation of a SpinChem rotating bed reactor further intensified the enzymatic process, leading to dramatically shorter reaction times and increased overall productivity

Authors & Research Group

All authors are based at the School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin, China.

Corresponding authors:

  • Yunting Liu — SciProfiles · ORCID Tianjin Key Laboratory of Chemical Process Safety
  • Lihui Wang — ResearchGate Tianjin Modern Vocational Technology College

Team members:

SpinChem perspective

Scaling enzymatic synthesis for pharmaceutical applications is rarely straightforward. Enzymes are sensitive, substrates are often poorly soluble in water, and batch processing creates bottlenecks at every scale-up step. What makes this research valuable is that it addresses all three challenges simultaneously.

The deep eutectic solvent does more than improve substrate solubility: it stabilises the enzymes, reducing deactivation at concentrations that would otherwise be impractical. Immobilising the enzymes on DES-modified resin carriers yields stability which transfers into enzyme reusability across multiple reaction cycles. And when a SpinChem RBR is introduced into the system, the improved mass transfer reduces reaction times while productivity is increased.

For teams working on chiral halohydrin synthesis in the pharmaceutical sector, this combination offers a practical route to greener, scalable production. An E-factor of 8.3 also signals that this concept has genuine industrial potential in pharma.

—Erik Löfgren, CTO, SpinChem AB

Topics Scientific Literature, Biocatalysis

Products SpinChem® RBR S2