Abstract
Computational modelling of metabolic networks has become an established procedure in the metabolic engineering of production strains. One key principle that is frequently used to guide the rational design of microbial cell factories is the stoichiometric coupling of growth and product synthesis, which makes production of the desired compound obligatory for growth. Here we show that the coupling of growth and production is feasible under appropriate conditions for almost all metabolites in genome-scale metabolic models of five major production organisms. These organisms comprise eukaryotes and prokaryotes as well as heterotrophic and photoautotrophic organisms, which shows that growth coupling as a strain design principle has a wide applicability. The feasibility of coupling is proven by calculating appropriate reaction knockouts, which enforce the coupling behaviour. The study presented here is the most comprehensive computational investigation of growth-coupled production so far and its results are of fundamental importance for rational metabolic engineering.
Highlights
Computational modelling of metabolic networks has become an established procedure in the metabolic engineering of production strains
Mutant strain: Growth obligatorily coupled with product synthesis
To illustrate how the fluxes in a metabolic network are affected by a constrained minimal cut set (cMCS), we describe the effects of the found cMCS inducing growth-coupled production of shikimate in yeast under aerobic conditions
Summary
Computational modelling of metabolic networks has become an established procedure in the metabolic engineering of production strains. We show that the coupling of growth and production is feasible under appropriate conditions for almost all metabolites in genome-scale metabolic models of five major production organisms. These organisms comprise eukaryotes and prokaryotes as well as heterotrophic and photoautotrophic organisms, which shows that growth coupling as a strain design principle has a wide applicability. OptKnock[13] was the first optimization method proposed for computing reaction deletion strategies to couple the production of a metabolite to cellular growth This method can be seen as the origin of a variety of developed strain design methods for growth-coupled product syntheses[6,14,15,16]. An additional question is to what degree the growth-coupled synthesis of metabolites is feasible in other relevant production organisms
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
