Multiobjective Optimization of a Fed-Batch Bienzymatic Reactor for Mannitol Production

Enzymatic reactions can successfully replace complex chemical syntheses using milder reaction conditions and generating less waste. The developed model-based numerical analysis turned out to be a beneficial tool to determine the optimal operating policies of complex multienzymatic reactors. As proved, for such cases, the determination of a Fed-Batch Reactor (FBR) optimal operating policy results in a difficult multiobjective optimization problem. Exemplification is made for the bienzymatic reduction of D-fructose to mannitol by using MDH (mannitol dehydrogenase) and nicotinamide adenine dinucleotide (NADH) cofactor with the in situ continuous regeneration of NADH at the expense of formate degradation in the presence of FDH (formate dehydrogenase). For such a coupled system, the model-based engineering evaluations must account for multiple competing (opposable) optimization objectives. Among the multiple novelty elements: i) an optimally operated FBR with a tightly controlled variable feeding (of the time stepwise type) during the batch can lead to higher performance; ii) the optimally operated FBR reported better performance compared to an optimally single or cyclic BR, or to optimally serial batch-to-batch reactors (SeqBR), when considering a multiobjective optimization; iii) the concomitant variable feeding with substrate, enzymes, and cofactor during the FBR “time-arcs” is an option seldom approached in the literature but which is proved here, leading to consistent economic benefits.