Gene Deletion Algorithms for Minimum Reaction Network Design by Mixed-Integer Linear Programming for Metabolite Production in Constraint-Based Models: gDel_minRN
Gene Deletion Algorithms for Minimum Reaction Network Design by Mixed-Integer Linear Programming for Metabolite Production in Constraint-Based Models: gDel_minRN
复制标题
基于约束模型中代谢物生产的混合整数线性规划最小反应网络设计的基因删除算法：gDel_minRN
DOI：
10.1089/cmb.2022.0352
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发表时间：
2023
影响因子：
1.7
通讯作者：
Kosaka Tomoyuki
中科院分区：
文献类型：
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作者：
Tamura Takeyuki;Muto-fujita Ai;Tohsato Yukako;Kosaka Tomoyuki
基于基因组规模约束的代谢网络在生长耦合生产的模拟中发挥着重要作用，这意味着同时实现细胞生长和目标代谢产物的产生。对于生长耦合生产，已知基于最小反应网络的设计是有效的。然而，由于与基因-蛋白质-反应（GPR）关系相冲突，所获得的反应网络往往不能通过基因删除来实现。在这里，我们开发了gDel_minRN，它使用混合整数线性规划确定基因删除策略，通过GPR关系抑制最大反应数来实现生长耦合生产。计算实验的结果表明，gDel_minRN可以确定的核心部分，其中包括只有30%至55%的全基因，化学计量可行的生长耦合生产的许多目标代谢物，其中包括有用的维生素，如生物素（维生素B7），核黄素（维生素B2），和泛酸（维生素B5）。由于gDel_minRN计算基因相关反应的最小数量的基于约束的模型，而不与GPR关系冲突，因此它有助于对每种靶代谢物的生长耦合生产所必需的核心部分进行生物分析。在MATLAB中使用CPLEX和COBRA编译器实现的源代码可在https://github.com/MetNetComp/gDel-minRN上获得。
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.
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影响因子：
3
作者：
Patil, KR;Rocha, I;Förster, J;Nielsen, J
通讯作者：
Nielsen, J
影响因子：
14.8
作者：
Heirendt, Laurent;Arreckx, Sylvain;Fleming, Ronan M. T.
通讯作者：
Fleming, Ronan M. T.
影响因子：
5.8
作者：
Apaolaza, Inigo;Valcarcel, Luis Vitores;Planes, Francisco J.
通讯作者：
Planes, Francisco J.
什么是通量平衡分析？
影响因子：
46.9
作者：
通讯作者：
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