Genome-scale metabolic reconstructions are well established for in silico analysis and design of microbial cell factories. By contrast, fermentation processes are typically described with unstructured models containing phenomenological descriptions of nutrient uptake, cellular growth and product secretion. While unstructured fermentation models are relatively easy to formulate and solve, they lack a fundamental biochemical basis upon which to build high fidelity bioreactor simulations that are extensible to new process conditions. In Silico Fermentation provides state-of-art capabilities for integrating metabolic reconstructions into bioreactor simulations such that the same metabolic strain model can be used across your research, development and manufacturing organizations.
Stirred Tank Bioreactors
Stirred tank bioreactors in which cells are suspended in the liquid medium are the most common type of microbial fermenters. We have pioneered the development of stirred tank bioreactor models in which metabolic reconstructions of single strains or synthetic communities are embedded within dynamic mass balances equations for the extracellular environment. Such dynamic flux balance models allow time-resolved concentration predictions of supplied nutrients, cellular biomass and secreted products that can be compared directly to experimental measurements. Our STBRsim app implements a complete workflow for formulation and simulation of stirred tank bioreactor models based on metabolic reconstructions, including the specification of non-metabolic regulatory effects such as catabolite repression and product inhibition.
Spatially Varying Bioreactors
Several types of bioreactors are specifically designed to create spatial gradients that generate favorable local environments for nutrient consumption, cellular growth and/or product synthesis. For example, bubble column bioreactors with countercurrent flows of the liquid medium and gaseous feed can generate regions of high dissolved gas and low inhibitory product concentrations that facilitate cellular growth and product formation. Similarly, biofilm bioreactors can be engineered to take advantage of concentration gradients along the biofilm. We have considerable experience embedding metabolic reconstructions within diffusion-convection equations to generate bubble column models and biofilm models that generate both temporal and spatial concentration predictions that can be utilized for bioreactor design, operation and optimization.
Please reach out to discuss your fermentation modeling needs.
