Metabolic engineering is defined as improving the cellular activities of an organism by manipulating the metabolic, signal or regulatory network. In silico reaction knockout simulation is one of the techniques applied to analyse the effects of genetic perturbations on metabolite production. Many methods consider growth coupling as the objective function, whereby it searches for mutants that maximise the growth and production rate. However, the final goal is to increase the production rate. Furthermore, they produce one single solution, though in reality, cells do not focus on one objective and they need to consider various different competing objectives. In this work, a method, termed ndsDSAFBA (non-dominated sorting Differential Search Algorithm and Flux Balance Analysis), has been developed to find the reaction knockouts involved in maximising the production rate and growth rate of the mutant, by incorporating Pareto dominance concepts. The proposed ndsDSAFBA method was validated using three genome-scale metabolic models. We obtained a set of non-dominated solutions, with each solution representing a different mutant strain. The results obtained were compared with the single objective optimisation (SOO) and multi-objective optimisation (MOO) methods. The results demonstrate that ndsDSAFBA is better than the other methods in terms of production rate and growth rate.
The metabolic network is the reconstruction of the metabolic pathway of an organism that is used to represent the interaction between enzymes and metabolites in genome level. Meanwhile, metabolic engineering is a process that modifies the metabolic network of a cell to increase the production of metabolites. However, the metabolic networks are too complex that cause problem in identifying near-optimal knockout genes/reactions for maximizing the metabolite's production. Therefore, through constraint-based modelling, various metaheuristic algorithms have been improvised to optimize the desired phenotypes. In this paper, PSOMOMA was compared with CSMOMA and ABCMOMA for maximizing the production of succinic acid in E. coli. Furthermore, the results obtained from PSOMOMA were validated with results from the wet lab experiment.
In recent years, metabolic engineering has gained central attention in numerous fields of science because of its capability to manipulate metabolic pathways in enhancing the expression of target phenotypes. Due to this, many computational approaches that perform genetic manipulation have been developed in the computational biology field. In metabolic engineering, conventional methods have been utilized to upgrade the generation of lactate and succinate in E. coli, although the yields produced are usually way below their theoretical maxima. To overcome the drawbacks of such conventional methods, development of hybrid algorithm is introduced to obtain an optimal solution by proposing a gene knockout strategy in E. coli which is able to improve the production of lactate and succinate. The objective function of the hybrid algorithm is optimized using a swarm intelligence optimization algorithm and a Simple Constrained Artificial Bee Colony (SCABC) algorithm. The results maximize the production of lactate and succinate by resembling the gene knockout in E. coli. The Flux Balance Analysis (FBA) is integrated in a hybrid algorithm to evaluate the growth rate of E. coli as well as the productions of lactate and succinate. This results in the identification of a gene knockout list that contributes to maximizing the production of lactate and succinate in E. coli.