Advances in the Process Development of Biocatalytic Processes

Abstract

Biocatalysis is already established in chemical synthesis on an industrial scale, in particular in the pharmaceutical sector. However, the wider implementation of biocatalysis is currently hindered by the extensive effort required to develop a competitive process. In order that resources spent on development are used in the most efficient manner for these challenging systems, a holistic view on process development and a more in-depth understanding of the underlying constraints (process related as well as biocatalyst related) are required. In this concept article a systematic approach to solve this problem is proposed, involving the use of process tools and methods to assist in development.

A Microfluidic Toolbox for the Development of In-Situ Product Removal Strategies in Biocatalysis

“…Important to emphasize is that ISPR implementation will not change the requirements of the overall process to fulfill specific metrics for economic feasibility. For example, it will still be required to reach specific overall process targets exiting the ISPR configuration, such as certain product titers ( g P =L ), reaction yield (%), biocatalyst yield g P =g biocat ð ), or space-time yields (STY) g P =L=h ð ) [26]. High product titers exiting the ISPR configuration are important in terms of how costly the following DSP will be.…”

“…ISPR Separation Strategies. The choice of ISPR separation strategy is commonly based upon exploiting differences in the physicochemical properties of the involved reaction species [26]. Thus, one approach is to exploit conventional separation principles as ISPR/IScPR strategies, which is closely linked to the DSP.…”

Biocatalytic process development using microfluidic miniaturized systems

“…While in nature, enzymes usually catalyze thermodynamically favorable reactions, for non-natural substrates as well as reactions run in synthetic mode, this is frequently not the case. Thus, the design of any process needs to also consider the likely operating space for the biocatalyst and the implication of changing key parameters on the process feasibility and cost [4].…”

“…This presents an interesting challenge for process chemists and engineers, since the wish to implement a new (non-natural) substrate at high concentrations can only be addressed by a concerted development effort with a combination of biocatalyst modification and process modification. The driver for such process development is economic and while targets can be evaluated in a given case, there remains a further problem, because there are many options to choose from and different routes to solve a given problem [4]. While some solutions are more effective than others, and some are easier to implement than others, there remain many choices to be made.…”

Simultaneous Multienzymatic Screening with Fluorogenic Probes

“…13 In the case of microplate assays, this allows the simultaneous and parallel monitoring of different biomolecules in a single system, paving the way for different and wider applications within the current biological context, such as the discovery of new biocatalysts of interest with the use of specific fluorogenic/chromogenic probes. 4,[14][15][16][17] The inclusion of biocatalytic steps in predominantly chemical processes is an excellent alternative to improve parameters such as reaction conversion and selectivity; 15 or even more complex cases, when it is aimed at obtaining a biocatalyst able to catalyze different substrates (enzymatic promiscuity). 18,19 To that end, genetic engineering techniques have been used to improve catalytic potential through directed evolution processes.…”