Conceptual Process Design in Fermentation-Based Biomanufacturing

The transition towards more sustainable production patterns as postulated in the 2030 Sustainable Development Agenda of the United Nations is one of the major challenges of our generation. In the wake of this transition, implementing fermentation-based biomanufacturing processes to replace the current chemical manufacturing processes is a key element. Nonetheless, major obstacles for the conceptual design of fermentation-based biomanufacturing processes remain. An example of these biomanufacturing processes are second-generation biorefineries. They utilize lignocellulosic biomass to produce different chemicals, fuels, energy, or materials. Despite their vast potential and dedicated research toward them over the past decades, the number of commercially operating plants is low and falls short of expectations. This is mainly due to their deficient economic potential.


In the light of the elaborated status quo and reviews on biomanufacturing, biorefinery concepts, and process design methodologies in the scope of this thesis, four research questions are formulated and investigated. For this, a case study for xylitol production in a biomanufacturing process is selected. The objective is to design the process for such a second-generation biorefinery conceptually and to investigate both the economic potential and the sustainability impact of the process in order to draw specific conclusions for the case study. Based on the results, conclusions and recommendations for future work regarding the conceptual process design of fermentation-based biomanufacturing processes from a more general perspective are formulated.


The first research question addresses the biomass pretreatment, which is an essential unit operation in the upstream process to fractionate and depolymerize the lignocellulosic biomass to use the monomers for the subsequent fermentation. After defining criteria for the fractionation and depolymerization, the two most promising out of all potential candidates of pretreatment technologies are selected, and experiments are designed and performed. Based on the results, the criteria for both investigated pretreatment methodologies are evaluated.


The second research question addresses the need for a suitable computational framework for the conceptual process design. Based on the evaluation of the shortcomings of the three most widespread design methodologies, namely heuristics and expert knowledge-based design, superstructure optimization, and simulation-based optimization, a synergistic optimization-based framework is proposed. An essential part of the framework is the use of surrogate models to enhance the computational tractability of the optimization. Different surrogate models are validated, and their metrics are compared to assess the framework. Based on this, the framework is applied to a case study to benchmark the different surrogate models and ultimately validate the framework regarding its suitability for the conceptual process design of biomanufacturing processes.


The third research question addresses the economic feasibility of a potential biomanufacturing process for xylitol production in a second-generation biorefinery setup. To begin with the end in mind, the production of value-added co-products apart from xylitol is considered, as well as the potential of process integration through the internal production of steam and electricity to increase the economic feasibility. Mechanistic models for all potentially employed unit operations are developed and assessed. With the previously introduced framework, the biorefinery process is then designed. Based on the results, a risk-based economic analysis is performed to assess the impact of uncertainties in the capital expenditures, the operational expenses, and the market prices for the products, allowing for a conclusion regarding the economic feasibility of the biorefinery process.


Lastly, the fourth research question addresses the sustainability impact of the designed biorefinery process. A standardized four-step life cycle assessment for the plant is performed. The first step involves defining the assessment's goal, scope, and boundaries. In the second step, the assessment inventory subsumes all relevant flows going in and out of the system. The third step characterizes the impacts of each flow in respective impact categories that are defined through the choice of a specific impact assessment methodology. After normalizing the characterization results to a reference point, in the fourth step, the assessment results are interpreted. Furthermore, based on available life cycle assessment data from the current chemical production processes of xylitol, the process is compared to two different commercial alternatives, allowing for a conclusion regarding the sustainability impact of the biorefinery process.


Lastly, by answering the four research questions, the case study is evaluated as a whole, and potential strategies for improvement are indicated. By taking into account the results from this work, the developments in synthetic biology, and the fourth industrial revolution, a blueprint of a future design strategy for fermentation-based biomanufacturing processes is given to expedite the transition towards more sustainable production patterns.