Metabolic modelling in the development of cell factories by synthetic biology

Abstract

Cell factories are commonly microbial organisms utilized for bioconversion of renewable resources to bulk or high value chemicals. Introduction of novel production pathways in chassis strains is the core of the development of cell factories by synthetic biology. Synthetic biology aims to create novel biological functions and systems not found in nature by combining biology with engineering. The workflow of the development of novel cell factories with synthetic biology is ideally linear which will be attainable with the quantitative engineering approach, high-quality predictive models, and libraries of well-characterized parts. Different types of metabolic models, mathematical representations of metabolism and its components, enzymes and metabolites, are useful in particular phases of the synthetic biology workflow. In this minireview, the role of metabolic modelling in synthetic biology will be discussed with a review of current status of compatible methods and models for the in silico design and quantitative evaluation of a cell factory.

Keywords: chassis; constraint-based; flux; kinetics; simulation.

Figure 1

Workflow of the development of a cell factory with synthetic biology. The workflow of the development of a novel cell factory with synthetic biology is divided in three main phases: the design phase, the experimental phase and the phase of the quantitative evaluation of the novel strain. Metabolic modelling is involved in the design and quantitative evaluation phases. Albeit the aim for linearity in the workflow, simulated behaviour of the in silico strain or in vivo behaviour of the novel strain may force return to previous steps.

Figure 2

Metabolic models involved in the development of cell factories with synthetic biology. The four metabolic modelling approaches involved in the workflow of the development of a cell factory with synthetic biology are shown in an order of increasing complexity from topological to constraint-based, atom-mapped, and kinetic models. The phases and the tasks of the synthetic biology workflow, where the particular models are used, are shown below the descriptions of the types of the models.