Optimizing biocatalyst blend distribution for continuous fructose production in a packed bed reactor

The continuous production of high-fructose syrup using immobilized enzymes (β[jls-end-space/]-galactosidase and glucose isomerase) in packed-bed reactors (PBR) presents challenges due to conflicting kinetic properties and thermal deactivation rates. To address these limitations, this work proposes a novel reactor design strategy based on the simultaneous spatial optimization of the catalyst blend ratio and temperature profile, coupled with dynamic flow control. A rigorous mathematical model, discretized via the Method of Lines and solved using a Non-Linear Programming (NLP) framework, was developed to maximize fructose productivity over the catalyst lifespan. Two control strategies were evaluated: a conventional uniform temperature control approach and the proposed spatially distributed strategy. Results show that spatially decoupling the thermal and catalytic conditions along the reactor axis overcomes inherent kinetic trade-offs between the two enzymes. The optimizer identifies two distinct zones of the reactor: an initial low-temperature region dominated by β[jls-end-space/]-galactosidase for lactose hydrolysis, followed by a high-temperature region rich in glucose isomerase for isomerization. This distributed configuration, transitioning from prioritizing the stability of the thermosensitive enzyme to promoting kinetic activation, yielded a 13.4% increase in fructose concentration compared to optimal uniform operation. While amplified by the large thermal stability difference between the two enzymes, the methodology remains applicable to systems with smaller stability contrasts, where spatial decoupling provides a rational basis for overcoming reaction bottlenecks. The proposed methodology offers a versatile tool for the rational design of heterogeneous biocatalytic processes constrained by stability and multi-step enzymatic cascades.