Biocatalysis is an emerging area of technology, and to date few reports have documented the economics of such processes. As it is a relatively new technology, many processes do not immediately fulfill the economic requirements for commercial operation. Hence, early-stage economic assessment could be a powerful tool to guide research and development activities in order to achieve commercial potential. This study discusses the cost contribution of the biocatalyst in processes that use isolated enzymes, immobilized enzymes, or whole cells to catalyze reactions leading to the production of chemicals. A methodology for rapidly estimating the production cost of the biocatalyst is presented, and examples of how the cost of the biocatalyst is affected by different parameters are given. In particular, it is seen that the fermentation yield in terms of final achievable cell concentration and expression level as well as the production scale are crucial for decreasing the total cost contribution of the biocatalyst. Moreover, it is clear that, based on initial process performance, the potential to reduce production costs by several orders of magnitude is possible. Guideline minimum productivities for a feasible process are suggested for different types of processes and products, based on typical values of biocatalyst and product costs. Such guidelines are dependent on the format of the biocatalyst (whole-cell, soluble enzyme, immobilized enzyme), as well as product market size and value. For example commodity chemicals require productivities in the range 2000-10000 kg product/kg immobilized enzyme, while pharmaceutical products only require productivities around 50-100 kg product/kg immobilized enzyme.
Biocatalytic transamination is being established as key tool for the production of chiral amine pharmaceuticals and precursors due to its excellent enantioselectivity as well as green credentials. Recent examples demonstrate the potential for developing economically competitive processes using a combination of modern biotechnological tools for improving the biocatalyst alongside using process engineering and integrated separation techniques for improving productivities. However, many challenges remain in order for the technology to be more widely applicable, such as technologies for obtaining high yields and productivities when the equilibrium of the desired reaction is unfavorable. This review summarizes both the process challenges and the strategies used to overcome them, and endeavors to describe these and explain their applicability based on physiochemical principles. This article also points to the interaction between the solutions and the need for a process development strategy based on fundamental principles.
Abstract:The increasing industrial interest in biocatalytic processes is predominantly driven by the need for selective chemistry, with high reaction yield (Y reaction ) and few side reactions, as well as the need for optically pure chiral molecules (in particularly in the pharmaceutical industry). Interestingly, it is often argued that the mild conditions frequently used in biocatalytic reactions (ambient temperature and pressure, neutral pH and aqueous-based media) automatically lead to environmentally-friendly and cost-effective production processes. However, such a conclusion is not justified without the use of adequate tools to evaluate the performance of a process, in particular during process development. Nevertheless, at the early development stage, evaluation of biocatalytic processes is not a trivial task, not only due to the lack of data, but also because at this stage many of the biocatalytic processes are not yet fully optimized. Hence, in this paper we propose the use of a range of tools which can be used to guide process development, research tasks and support decision-making. Three sets of metrics are identified, each for use at different stages of process development (route selection, early development and late development), each with different objectives.
Previously, it could be demonstrated, that the monophasic, enzymatic reduction of aliphatic 2-ketones into the corresponding (R)-2-alcohols is an adequate and viable method as carried out in a cascade of two enzyme−membrane reactors (Leuchs, S.; Na'amnieh, S. N.; Greiner, L. Green Chemistry 2013, 15, 167−176.). In the present work, the process metrics of the ketone reduction were calculated. A cost analysis revealed that the enzyme costs are negligible, but the cost for nicotinamide cofactor NADP + is dominating the overall cost of the chemical raw material followed by the ionic liquid (TEGO IL K5) used as solubiliser and the buffer. The overall cost of chemicals was €148/kg product . To assess the environmental impact of the process, the E-factor (kg waste /kg product ) 132 and the process mass intensity 133 (PMI, kg substrate /kg product ) were calculated. A process model based on initial rate experiments was elaborated and used to improve the process under cost and environmental aspects. Applying several measures to enhance the cofactor utilisation, the cost base could be reduced by 65% and the E-factor (PMI) to 17 (18).
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