Using Spinchem Rotating Bed Reactor Technology for Immobilized Enzymatic Reactions: A Case Study

Abstract

The practically and financially viable use of immobilized enzymes in the production of pharmaceutical and bulk chemicals requires highly catalytically active enzymes and efficient mass transfer of substrate to the active site. The substantial cost of immobilized enzymes further mandates extended reuse of the enzymes to keep operating expenditures down. The extent of reuse of immobilized enzymes depends on parameters such as enzyme long-term stability under process conditions, carrier integrity and attrition due to mechanical stress, and ease of workup and recovery on scale. Herein, we report on the use of a SpinChem rotating bed reactor (RBR) for the Novozyme 435 mediated kinetic resolution of (cis)-isopropyl 3aminocyclohexanecarboxylate as an alternative to the traditional reaction using free-flowing immobilized lipases in an ordinary batch reactor. Reusability was studied in addition to other parameters such as type of immobilized enzyme, loading, rate of agitation, temperature, and scalability. By using SpiChem RBR technology, we found that recycling of the immobilized enzyme was easy with preserved enantioselectivity and catalytic activity. The final optimized process was successfully demonstrated on a 1 kg scale with 39% isolated yield and 98.8% enantiomeric purity.

Enzymatic synthesis of novel aromatic‐aliphatic polyesters with increased hydroxyl group density

“…An aluminum tissue was used to jacket the stirrer and confine the biocatalyst. Whereas the idea of a rotating bed reactor has been developed and commercialized previously, [ 39,40 ] the optimizing of the mixing conditions is the focus of the present set‐up. Mixing of the reactants was visibly improved with respect to the flask and oligomerization was already obtained within 24 h at 50°C.…”

“…An aluminum tissue was used to jacket the stirrer and confine the biocatalyst. Whereas the idea of a rotating bed reactor has been developed and commercialized previously, [39,40] the optimizing of the mixing conditions is the focus of the present set-up. Mixing of the reactants was visibly improved with respect to the flask and oligomerization was already obtained within 24 h at 50 • C. The analysis of the products obtained during the synthesis by end group titration and 1 H-NMR spectroscopy reveals that the reactor outperformed the standard synthesis in the flask.…”

Lipase-Catalyzed Production of Sorbitol Laurate in a “2-in-1” Deep Eutectic System: Factors Affecting the Synthesis and Scalability

“…Remarkably, Although our discussion mainly revolved around the use of rather conventional reactors, such as STRs for batch heterogenous biocatalysis, innovative and commercially available alternatives have risen on the market. The Rotating Bed Reactors (RBRs), notably commercialized by the SpinChem company (www.spinchem.com, Tvistevägen, Sweden), have proven to be promising alternatives to STRs and have shown good results when used for immobilized enzymatic reactions [75]. Furthermore, their cooperation with Purolite (www.purolite.com, King of Prussia, PA, USA) gave light to immobilized lipase cartridges, theoretically forming a rotating packed bed reactor, which removes the need for filtration during the DSP and simplifies the recovery of the biocatalyst.…”

Catalytic Functionalized Structured Monolithic Micro-/Mesoreactors: Engineering, Properties, and Performance in Flow Synthesis: An Overview and Guidelines

“…So far, the RBR baskets were mostly packed with common particulate (bio)catalysts, for example, Novozym 435 (Pithani et al, 2019), provided the size was larger than 0.4-0.5 mm. However, to make full use of RBR potentials to improve reaction kinetics, we proposed to load the basket with larger catalytic pellets/beads, a few millimeters in size, but with a hierarchical pore structure, as in the M-monoliths (vide supra) (Szymańska et al, 2017).…”