Gene Deletion Algorithms for Minimum Reaction Network Design by Mixed-Integer Linear Programming for Metabolite Production in Constraint-Based Models: gDel_minRN.
J Comput Biol
; 30(5): 553-568, 2023 05.
Article
in En
| MEDLINE
| ID: mdl-36809057
ABSTRACT
Genome-scale constraint-based metabolic networks play an important role in the simulation of growth-coupled production, which means that cell growth and target metabolite production are simultaneously achieved. For growth-coupled production, a minimal reaction-network-based design is known to be effective. However, the obtained reaction networks often fail to be realized by gene deletions due to conflicts with gene-protein-reaction (GPR) relations. Here, we developed gDel_minRN that determines gene deletion strategies using mixed-integer linear programming to achieve growth-coupled production by repressing the maximum number of reactions via GPR relations. The results of computational experiments showed that gDel_minRN could determine the core parts, which include only 30% to 55% of whole genes, for stoichiometrically feasible growth-coupled production for many target metabolites, which include useful vitamins such as biotin (vitamin B7), riboflavin (vitamin B2), and pantothenate (vitamin B5). Since gDel_minRN calculates a constraint-based model of the minimum number of gene-associated reactions without conflict with GPR relations, it helps biological analysis of the core parts essential for growth-coupled production for each target metabolite. The source codes, implemented in MATLAB using CPLEX and COBRA Toolbox, are available on https//github.com/MetNetComp/gDel-minRN.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Programming, Linear
/
Models, Biological
Language:
En
Journal:
J Comput Biol
Journal subject:
BIOLOGIA MOLECULAR
/
INFORMATICA MEDICA
Year:
2023
Document type:
Article
Affiliation country: