Abstract

Multi-enzymatic reactions can successfully replace complex chemical syntheses, using milder reaction conditions, and generating less waste. The present model-based analysis compares the performances of several optimally operated Batch Reactors (BR) with those of an optimally operated serial Sequence of BRs (SeqBR). In multi-enzymatic systems, SeqBR could be more advantageous and flexible, allowing the optimization of costly enzymes amounts used in each BR in the series. Exemplification was made for the bi-enzymatic reduction of D-fructose to mannitol by using MDH (mannitol dehydrogenase) and the 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 coupled enzymatic systems, the model-based engineering evaluations are difficult tasks, because they must account for the common species’ initial levels, their interaction, and their dynamics. The determination of optimal operating modes of sole BR or of a SeqBR turns into a multi-objective optimization problem with multiple constraints to be solved for every particular system. The study presents multiple elements of novelty: (i) the proof of higher performances of an optimal SeqBR (including N-BRs) compared to a sole optimal BR operated for N-number of runs and (ii) the effect of using a multi-objective optimization criteria on SeqBR adjustable dynamics.

Highlights

  • Model-Based Optimization of Mannitol Production by Using a Sequence of Batch Reactors for a Coupled Bi-Enzymatic Process—A

  • The direct comparison is made between the sole optimal Batch Reactors (BR) and one run of an optimally operated Sequence of BRs (SeqBR) including a series of the same number of 10 BR, of the same size, but each BR operated in a different way

  • Such a direct comparison between a sole BR repeatedly operated 10× with the same optimal initial conditions and an optimal SeqBR with the same number of BRs operated only one time is justified because the three optimization objectives explained in Section 3.2 and in Section 4.3 are basically the same, even if the optimized operating policy is obtained by applying different algorithms

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Summary

Introduction

Model-Based Optimization of Mannitol Production by Using a Sequence of Batch Reactors for a Coupled Bi-Enzymatic Process—A. The present model-based analysis compares the performances of several optimally operated Batch Reactors (BR) with those of an optimally operated serial Sequence of BRs (SeqBR). Exemplification was made for the bi-enzymatic reduction of D-fructose to mannitol by using MDH (mannitol dehydrogenase) and the 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 coupled enzymatic systems, the model-based engineering evaluations are difficult tasks, because they must account for the common species’ initial levels, their interaction, and their dynamics. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations

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