Metabolites production improvement by identifying minimal genomes and essential genes using flux balance analysis.

Pub Date : 2015-01-01 DOI:10.1504/ijdmb.2015.068955
Abdul Hakim Mohamed Salleh, Mohd Saberi Mohamad, Safaai Deris, Rosli Md Illias
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Abstract

With the advancement in metabolic engineering technologies, reconstruction of the genome of host organisms to achieve desired phenotypes can be made. However, due to the complexity and size of the genome scale metabolic network, significant components tend to be invisible. We proposed an approach to improve metabolite production that consists of two steps. First, we find the essential genes and identify the minimal genome by a single gene deletion process using Flux Balance Analysis (FBA) and second by identifying the significant pathway for the metabolite production using gene expression data. A genome scale model of Saccharomyces cerevisiae for production of vanillin and acetate is used to test this approach. The result has shown the reliability of this approach to find essential genes, reduce genome size and identify production pathway that can further optimise the production yield. The identified genes and pathways can be extendable to other applications especially in strain optimisation.

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通过通量平衡分析鉴定最小基因组和必需基因来改善代谢物的产生。
随着代谢工程技术的进步,可以重建宿主生物的基因组以获得所需的表型。然而,由于基因组尺度代谢网络的复杂性和规模,重要成分往往是不可见的。我们提出了一种改善代谢物产生的方法,包括两个步骤。首先,我们使用通量平衡分析(FBA)通过单个基因缺失过程找到必需基因并鉴定最小基因组,其次通过基因表达数据确定代谢物产生的重要途径。用于生产香兰素和醋酸盐的酿酒酵母的基因组规模模型被用来测试这种方法。结果表明,这种方法在寻找必需基因、减小基因组大小和确定生产途径方面是可靠的,可以进一步优化产量。鉴定的基因和途径可以扩展到其他应用,特别是在菌株优化。
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