Multiscale modelling of bioprocess dynamics and cellular growth

Camilo Mahnert, Diego A. Oyarzún, Julio Berrios*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Background
Fermentation processes are essential for the production of small molecules, heterologous proteins and other commercially important products. Traditional bioprocess optimisation relies on phenomenological models that focus on macroscale variables like biomass growth and protein yield. However, these models often fail to consider the crucial link between macroscale dynamics and the intracellular activities that drive metabolism and proteins synthesis.

Results
We introduce a multiscale model that not only captures batch bioreactor dynamics but also incorporates a coarse-grained approach to key intracellular processes such as gene expression, ribosome allocation and growth. Our model accurately fts biomass and substrate data across various Escherichia coli strains, efectively predicts acetate dynamics and evaluates the expression of heterologous proteins. By integrating construct-specifc parameters like promoter strength and ribosomal binding sites, our model reveals several key interdependencies between gene expression parameters and outputs such as protein yield and acetate secretion.

Conclusions
This study presents a computational model that, with proper parameterisation, allows for the in silico analysis of genetic constructs. The focus is on combinations of ribosomal binding site (RBS) strength and promoters, assessing their impact on production. In this way, the ability to predict bioreactor dynamics from these genetic constructs can pave the way for more efcient design and optimisation of microbial fermentation processes, enhancing the production of valuable bioproducts.
Original languageEnglish
Article number315
Pages (from-to)1-15
Number of pages15
JournalMicrobial Cell Factories
Volume23
Issue number1
DOIs
Publication statusPublished - 22 Nov 2024

Keywords / Materials (for Non-textual outputs)

  • multiscale modelling
  • fermentation process optimisation
  • Escherichia coli
  • gene expression dynamics
  • heterologous protein production
  • computational bioprocess design
  • intracellular modelling
  • metabolic engineering

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