While genome-scale metabolic reconstructions are routinely used as a computational platform for microbial strain analysis and design, their incorporation within process-oriented dynamic models is less common. Using dynamic extensions of flux balance analysis, metabolic reconstructions can be embedded within dynamic descriptions of the extracellular environment to develop simulation models of stirred tank bioreactors for predicting and enhancing fermentation performance. To effectively utilize these dynamic models, users must have adequate understanding of the bioreactor model structure, the adjustable model parameters, and the computational methods used for model solution. Without such knowledge, users often struggle to generate successful simulation runs, interpret simulation results, and to understand steady-state and dynamic trends as model parameters are varied.

To address these issues, In Silico Fermentation has developed a training course focused on the use of dynamic flux balance models for stirred tank bioreactor simulation. The training provides functional coverage of the underling models and computational methods while emphasizing the formulation and solution of practical problems using our MATLAB app STBRsim. The app workflow is demonstrated through efficient computational exercises using a small-scale model of Escherichia coli metabolism. Participants are encouraged to formulate and solve a stirred tank bioreactor simulation problem with a genome-scale metabolic reconstruction of their choice with assistance from the instructor as necessary. Each participant completes the course with a fully configured app and the hand-on experience necessary to utilize bioreactor simulations in their future bioprocess development efforts.

The training is specifically designed for on-line delivery in time blocks defined by the participants to maximize work flexibility and information retention. The full course with interactive exercises can be covered in no more than 24 on-line hours, while abbreviated versions presented focused exclusively on app usage can be completed in as little as 8 on-line hours. The course can be offered to 6-12 individual registrants or directly to employees from a single organization to allow a more customized training experience.

Course Topics

1. Formulation of stirred-tank bioreactor models using metabolic reconstructions

2. Modeling non-metabolic inhibitory effects between extracellular variables

3. Specification of bioreactor model parameters from available data

4. Dynamic simulation of bioreactor models with embedded metabolic reconstructions

5. Utilizing STBRsim for stirred-tank bioreactor simulation

6. Individualized STBRsim problem formulation and solution

Course participants are expected to have completed the training course Metabolic Models and Constraint-Based Analysis. Also recommended is practical experience with:

1. Stirred-tank bioreactors

2. Ordinary differential equations

Please contact us by email if you would like to learn more about this training course.