Application of modeling and simulation tools for the evaluation of biocatalytic processes: A future perspective

Abstract

Modeling and simulation techniques have for some time been an important feature of biocatalysis research, often applied as a complement to experimental studies. In this short review, we report on the state-of-the-art process and kinetic modeling for biocatalysis with the aim of identifying future research needs. We have particularly focused on four aspects of modeling: (i) the model purpose, (ii) the process model boundary, (iii) the model structure, and (iv) the model identification procedure. First, one finds that most of the existing models describe biocatalyst behavior in terms of enzyme selectivity, mechanism, and reaction kinetics. More recently, work has focused on extending these models to obtain process flowsheet descriptions. Second, biocatalysis models remain at a relatively low level of complexity compared with the trends observed in other engineering disciplines. Hence, there is certainly room for additional development, i.e., detailed mixing and hydrodynamics, more process units (e.g., biorefinery). Third, biocatalysis models have been only partially subjected to formal statistical analysis. In particular, uncertainty analysis is needed to ascertain reliability of the predictions of the process model, which is necessary to make sound engineering decisions (e.g., the optimal process flowsheet, control strategy, etc). In summary, for modeling studies to be more mature and successful, one needs to introduce Good Modeling Practice and that asks for (i) a standardized and systematic guideline for model development, (ii) formal identifiability analysis, and (iii) uncertainty analysis. This will advance the utility of models in biocatalysis for more rigorous application within process design, optimization, and control strategy evaluation. V

Immobilization of lipases on hydrophobic supports: immobilization mechanism, advantages, problems, and solutions

“…For this reason, the resolution of racemic mixtures of acids, alcohols, esters, amines or amides, or rather the desymetrization of this type of compounds bearing a prochiral centre, is a very usual process catalyzed by lipases (Cunha et al, 2015;de Miranda et al, 2015;Hoyos et al, 2016;Patel, 2012;Rodríguez-Mata and Gotor-Fernández, 2015;Seddigi et al, 2017). It is worth mentioning that going deeper into the knowledge of the molecular basis explaining the stereochemical recognition of (pro)chiral substrates is also a very attractive research area (Colombo et al, 2000;Cygler et al, 1994;Juhl et al, 2009;Li et al, 2008Li et al, , 2015Park et al, 2009;Rahman et al, 2012;Sin et al, 2009;Toledo et al, 2016;Trodler et al, 2009;Trodler and Pleiss, 2008).…”

Engineering a Seven Enzyme Biotransformation using Mathematical Modelling and Characterized Enzyme Parts

“…Indeed, in developing new biocatalytic processes the use of kinetic modelling is widely advocated, yet often not used in process development . The development of a kinetic model early on in the development process can be invaluable in cost/benefit or feasibility analysis .…”

“…Indeed, in developing new biocatalytic processes the use of kinetic modelling is widely advocated, yet often not used in process development . The development of a kinetic model early on in the development process can be invaluable in cost/benefit or feasibility analysis . It permits evidence‐based decision‐making, and critically allows for the identification of bottlenecks and the quantification of process problems (e. g. feedback inhibition or inhibition by side‐products) .…”

Process analytical technology (PAT) for biopharmaceuticals

“…Recent applications of mechanistic models for bio-based processes, such as biocatalysis [23] and fermentation [24] witnessed an interesting development. It should be emphasized indeed that the application of mechanistic modeling is not only relevant for the pharmaceutical industry, but also for fermentation and biocatalytic processes.…”