Efficient microbial production processes are essential for sustainable biomanufacturing,yet optimizing strain performance and bioreactor conditions remains challenging due tothe complex interplay between cellular metabolism and process parameters. Processesinvolving hydrogen-oxidizing bacteria (HOB), such as Xanthobacter sp. SoF1, are par-ticularly challenging due to limitations in gas–liquid mass transfer throughout the reac-tor.This study leverages constraint-based models of microbial metabolism to gain a deeperunderstanding of food-grade heterologous protein production by Xanthobacter sp.SoF1, predict cellular responses under bioreactor conditions, and assess how strainand process design choices influence performance and cost-effectiveness.Metabolic modeling is combined with simulations of various process conditions to iden-tify metabolic bottlenecks and key response patterns. Furthermore, a techno-economicassessment is used to identify target productivities and titers for an economically feasi-ble production process. The effect of different production scenarios on the strain perfor-mance and the economic feasibility serves as a basis for decisions in the envisionedbioprocess. By systematically mapping metabolic responses to process variations, thiswork provides a framework to connect the different scales affecting bioprocesses. Theresult of this framework are actionable insights for designing more efficient and cost-ef-fective microbial production systems. Furthermore, it guides rational decision-making instrain development and bioprocess optimization.
Sugiarto et al. (Mon,) studied this question.