Separation and Recovery of Intracellular Beta-Carotene Using a Process Synthesis Framework with Targeted Experiments

Abstract

Systematic process synthesis approaches are widely applied to traditional chemical process industries, but have seen limited use in the bioprocessing industry due to the limited or non-existent availability of thermodynamic or kinetic data. In this work, the process synthesis problem for the bio-manufacturing of high-value intracellular compounds is addressed using a systematic framework that allows for the user to input key process parameters from literature or experiments. The framework is based on a superstructure optimization approach and integrates various methods and tools, including a generic model and a database for data management. We propose the following five steps: (1) problem formulation, (2) data collection and superstructure generation, (3) solution of the optimization problem, and (4) process parameter analysis and (5) experimentation with informed design and then determination of the optimal process design. The framework is implemented in Super-O, software which guides the user through the formulation and solution of synthesis problems. This thesis demonstrates the proposed framework though an illustrative case study on the production of beta-carotene from recombinant Saccharomyces cerevisiae (SM14) via continuous cultivation using experimental, simulation and literature values.