Multi‐enzyme cascade reaction in a miniplant two‐phase‐system: Model validation and mathematical optimization

Abstract

Biotechnological application of multiple enzymes in different phases for target compounds synthesis poses a significant challenge for industrial process development. At the same time, a growing demand for natural flavors and fragrances opens up possibilities for novel biotechnological processes to replace current chemical synthesis routes, with additional advantages such as avoiding harsh reaction conditions and toxic chemicals, and less by-products in the system. Within complex biotechnological processes, the key for unfolding their industrial application potential in bioprocess engineering lies in their mathematical modeling. In this contribution, a multi-enzyme cascade reaction in a two-phase system implemented in a miniplant-scale reactor setup is mathematically modeled for the example of the flavoring agent cinnamyl cinnamate. Using our validated model and a mathematical optimization tool based on a genetic algorithm, optimization runs are performed to demonstrate the potential of computer-aided process development for complex biotechnological processes.

Pushing the boundaries of phosphorylase cascade reaction for cellobiose production II: Model‐based multiobjective optimization

“…Optimization of reaction variables (e.g., concentrations, concentration ratios, time) is rendered difficult technically because each parameter of efficiency of the overall transformation is composite of the interconnected outputs of the individual reactions telescoped in one pot (Kara & Rudroff, 2021; Siedentop et al, 2021). Optimization is even more complicated as it usually involves significant trade‐offs between multiple competing objectives (Dvorak et al, 2014; Johannsen et al, 2021; Paschalidis et al, 2022), such as maximum product yield and minimum enzyme usage, for example. Lastly, there can be substantial variation in the expectation of optimization capability, depending on the progress of process development and scale up (Teshima et al, 2023; Wang et al, 2020).…”

On the Use of the Adsorption Energy Distribution for the Analysis of Competing Substrate Kinetics

“…This means that the reaction performance alters due to the changes in the feedstock, and for each feedstock, an individual reaction model has to be applied. However, the knowledge of the correct (mathematical) characterization of the reaction kinetics and also of a subsequent separation process is necessary for the successful design of the whole processes and thus an important milestone for scale-up and industrial implementation. , …”

“…However, the knowledge of the correct (mathematical) characterization of the reaction kinetics and also of a subsequent separation process is necessary for the successful design of the whole processes and thus an important milestone for scale-up and industrial implementation. 8,9 The characterization of enzyme kinetics usually follows the same procedure, building either on an analysis of single reaction rates via the initial slope method or the analysis of a time series of concentrations via progress curve analysis. 10 In both cases, the change in the substrate or product concentration over time is measured experimentally and correlated with a suitable mathematical model.…”