BioRxiv
bioRxiv Subject Collection: Systems Biology
This feed contains articles for bioRxiv Subject Collection "Systems Biology"
OptEnvelope: a target point guided method for growth-coupled production using knockouts
Finding the best knockout strategy for coupling biomass growth and production of a target metabolite using a metabolic model is a challenge in biotechnology. In this research, a three-step method named OptEnvelope is developed based on finding minimal active reactions for a target point in the feasible solution space using a mixed-integer linear programming formula. The method initially finds the reduced desirable solution space (envelope) in the product versus biomass plot by removing all inactive reactions, and then, with reinsertion of the deleted reactions, OptEnvelope attempts to reduce the number of knockouts so that the production envelope is preserved. Additionally, OptEnvelope searches for envelopes with higher minimum product yields or fewer knockouts for different target points within the desired solution space. A number of knockouts can be set and evaluated using OptEnvelope in order to determine how it affects the intended envelope. The method was implemented on metabolic models of E. coli and S. cerevisiae to benchmark the capability of these industrial microbes for overproduction of acetate and glycerol under aerobic conditions and succinate and ethanol under anaerobic conditions. The results indicate that E. coli is more appropriate to produce acetate and succinate while S. cerevisiae is a better host for glycerol. The positive effect of deleting some genes responsible for the proposed reactions for knocking out was previously confirmed by reported experimental data. Both organisms are suitable for ethanol production, however, more knockouts for the adaptation of E. coli are required. OptEnvelope is available at https://github.com/lv-csbg/optEnvelope.
Motamedian, E., Berzins, K., Muiznieks, R., Stalidzans, E.
March 13, 2023
http://biorxiv.org/cgi/content/short/2023.03.10.532079v1?rss=1