A mechanistic-empirical model of central metabolism, signaling, and the reactor environment for bioprocesses
Conor O’Brien, and Wei-Shou Hu
Manual Contents:
1. Program description
2. Citation
3. Files in repository
4. Required software
5. Usage instructions

1. Program description

This model consists of mechanistic metabolic and reactor models with empirical cell signaling and growth models to simulate the complex dynamic that occur in suspension bioprocesses. In particular, it can be used to simulate and understand the metabolic shifts between lactate production and consumption which can occur during different stages of the fed-batch culture. It can be used to simulate different datasets by supplying a starting point, and key reactor and cell culture parameters can be changed to see the effect it has on the culture providing a straightforward method of in silico bioprocess simulation and optimization.

2. Citation

Paper citation:
Metab Eng. 2021 Apr 1;66:31-40. doi: 10.1016/j.ymben.2021.03.016

Depository citation:
O'Brien, Conor M; Hu, Wei-Shou. (2020). A mechanistic-empirical model of central metabolism, signaling, and the reactor environment for bioprocesses. Retrieved from the Data Repository for the University of Minnesota, https://doi.org/10.13020/kdqb-3023.

3. Files in repository

a) “bioprocessmodel.m”: This MATLAB file is a function consisting of the bioprocess model. It has several major sections corresponding to the different components of the model.
b) “modelsimulation.m”: This MATLAB script is where experimental data can be input and used initialize and call bioprocessmodel.m for simulation. In addition, key model parameters can be changed from this script to alter the behavior of the bioprocess model. After simulation, plots will automatically be generated. This is the file that should be run in MATLAB to simulate the model.
c) Readme: This file.

4. Required software

To run the model, MATLAB R2016b or later will be needed to run modelsimulation.m. If using an older version of MATLAB, one can place the functions into separate files.

5. Usage instructions

To run the model, example data has already been set up in the modelsimulation.m file. Make sure both the modelsimulation.m and the bioprocessmodel.m are in the same folder. To run the model, simply open modelsimulation.m file in MATLAB and run it. 


Simulation will automatically be performed and the results executed. 

If the user wishes to enter their own data, they can replace the section of the code to load in their own file containing the data, or simply enter it in the form shown in the code. The “index” and “totalLength” parameters should be updated to correspond to the data entered, as they are used to set the model parameter “KBP”. The example data consists of one run of the highest KBP and one of the lowest KBP, but intermediate runs may be added as well by adding values to the vector “index” between 1 and the “totalLength” value that the user may also set.

Additionally, there is a section for key model parameters which were set to achieve the variability in metabolic shifting to lactate production. These parameters may be modified to see what effect they may have on the culture.