Work

Modelling host biosynthetic limitations and dynamics for engineering cell factories

Year: 2026

Type: article

Abstract: Engineering microbes for chemical or protein production is a time-consuming iterative process of theoretical design, experimental construction, evaluation and redesign. A key cause of the failure of many initial designs is lack of consideration of host physiology. Here we summarise the key aspects of host physiology which are perturbed during metabolic engineering and synthetic biology projects and outline the implications of such host biosynthetic constraints and growth dynamics on engineered processes. We review how these phenomena can be captured in different modelling frameworks from traditional genome-scale approaches used for metabolic engineering to coarse-grain “host-aware” methods used in synthetic biology. We describe recent advances in whole-cell modelling. We give examples as to how these frameworks can be used to simplify the engineering biology design cycle and offer some open challenges in developing computer-aided design tools for engineering microbes.

Source: Critical Insights in Biotechnology

DOI: 10.1080/29932238.2026.2694307

Authors: Mohammad K. Khaleghi, William B. B. Hope, Christian Euler, Alexander P.S. Darlington

Institutions: University of Warwick, University of Waterloo

Language: English

Topic: Microbial Metabolic Engineering and Bioproduction

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Funders: Royal Academy of Engineering, University of Warwick, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council

Awards: Optimal cell factories for membrane protein production, Parameter identification with optimal experimental design for engineering biology, G3453850911, Combinatorial Biosynthetic Pathway Engineering, G7668798339