|Title||Risk-Based Bioengineering Strategies for Reliable Bacterial Vaccine Production|
|Author(s)||Kamminga, Tjerko; Slagman, Simen Jan; Martins dos Santos, Vitor A.P.; Bijlsma, Jetta J.E.; Schaap, Peter J.|
|Source||Trends in Biotechnology 37 (2019)8. - ISSN 0167-7799 - p. 805 - 816.|
Systems and Synthetic Biology
|Publication type||Refereed Article in a scientific journal|
|Keyword(s)||bacterial vaccines - constraint-based - genome-scale metabolic models - process analytical technology - risk-based process design|
Design of a reliable process for bacterial antigen production requires understanding of and control over critical process parameters. Current methods for process design use extensive screening experiments for determining ranges of critical process parameters yet fail to give clear insights into how they influence antigen potency. To address this gap, we propose to apply constraint-based, genome-scale metabolic models to reduce the need of experimental screening for strain selection and to optimize strains based on model driven iterative Design–Build–Test–Learn (DBTL) cycles. Application of these systematic methods has not only increased the understanding of how metabolic network properties influence antigen potency, but also allows identification of novel critical process parameters that need to be controlled to achieve high process reliability.