RatGene: Gene deletion-addition algorithms using growth to production ratio for growth-coupled production in constraint-based metabolic networks

Fuente: arXiv
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Auteurs principaux: Ma, Yier, Tamura, Takeyuki
Format: Preprint
Publié: 2024
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author Ma, Yier
Tamura, Takeyuki
author_facet Ma, Yier
Tamura, Takeyuki
contents In computational metabolic design, it is often necessary to modify the original constraint-based metabolic networks to lead to growth-coupled production, where cell growth forces target metabolite production. However, in genome-scale models, finding strategies to simultaneously delete and add genes to induce growth-coupled production is challenging. This is particularly true when heavy computation is necessary due to numerous gene deletions and additions. In this study, we mathematically defined related problems, proved NP-hardness and/or NP-completeness, and developed an algorithm named RatGene that (1) automatically integrates multiple constraint-based metabolic networks, (2) identifies gene deletion-addition strategies by a growth-to-production ratio-based approach, and (3) eliminates redundant gene additions and deletions. The results of computational experiments demonstrated that the RatGene-based approach can significantly improve the success ratio for identifying the strategies for growth-coupled production. RatGene can facilitate a more rational approach to computational metabolic design for the production of useful substances using microorganisms by concurrently considering both gene deletions and additions.
format Preprint
id arxiv_https___arxiv_org_abs_2411_12087
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle RatGene: Gene deletion-addition algorithms using growth to production ratio for growth-coupled production in constraint-based metabolic networks
Ma, Yier
Tamura, Takeyuki
Molecular Networks
Quantitative Methods
In computational metabolic design, it is often necessary to modify the original constraint-based metabolic networks to lead to growth-coupled production, where cell growth forces target metabolite production. However, in genome-scale models, finding strategies to simultaneously delete and add genes to induce growth-coupled production is challenging. This is particularly true when heavy computation is necessary due to numerous gene deletions and additions. In this study, we mathematically defined related problems, proved NP-hardness and/or NP-completeness, and developed an algorithm named RatGene that (1) automatically integrates multiple constraint-based metabolic networks, (2) identifies gene deletion-addition strategies by a growth-to-production ratio-based approach, and (3) eliminates redundant gene additions and deletions. The results of computational experiments demonstrated that the RatGene-based approach can significantly improve the success ratio for identifying the strategies for growth-coupled production. RatGene can facilitate a more rational approach to computational metabolic design for the production of useful substances using microorganisms by concurrently considering both gene deletions and additions.
title RatGene: Gene deletion-addition algorithms using growth to production ratio for growth-coupled production in constraint-based metabolic networks
topic Molecular Networks
Quantitative Methods
url https://arxiv.org/abs/2411.12087