2017/11/11 by Siu Hung Joshua Chan, Lin Wang, Chan, Siu Hung Joshua +5
Biochemistry, Genetics and Molecular Biology · Engineering · #Biofuel production and bioconversion #Enzyme Catalysis and Immobilization #FOS: Biological sciences #Microbial Metabolic Engineering and Bioproduction #Molecular Networks (q-bio.MN)
paper · pdf · doi:10.48550/arxiv.1711.04084
openalex publication_date 2017/11/11 · openalex created_date 2022/10/04 · openalex updated_date 2026/07/28
Background: Genome-scale metabolic network models and constraint-based\nmodeling techniques have become important tools for analyzing cellular\nmetabolism. Thermodynamically infeasible cy-cles (TICs) causing unbounded\nmetabolic flux ranges are often encountered. TICs satisfy the mass balance and\ndirectionality constraints but violate the second law of thermodynamics.\nCurrent prac-tices involve implementing additional constraints to ensure not\nonly optimal but also loopless flux distributions. However, the mixed integer\nlinear programming problems required to solve become computationally\nintractable for genome-scale metabolic models. Results: We aimed to identify\nthe fewest needed constraints sufficient for optimality under the loop-less\nrequirement. We found that loopless constraints are required only for the\nreactions that share elementary flux modes representing TICs with reactions\nthat are part of the objective function. We put forth the concept of localized\nloopless constraints (LLCs) to enforce this minimal required set of loopless\nconstraints. By combining with a novel procedure for minimal null-space\ncalculation, the computational time for loopless flux variability analysis is\nreduced by a factor of 10-150 compared to the original loopless constraints and\nby 4-20 times compared to the currently fastest method Fast-SNP with the\npercent improvement increasing with model size. Importantly, LLCs offer a\nscalable strategy for loopless flux calculations for\nmulti-compartment/multi-organism models of very large sizes (e.g. >104\nreactions) not feasible before. Matlab functions are available at\nhttps://github.com/maranasgroup/lll-FVA.\n