Mienda Bashir Sajo, Shamsir Mohd Shahir
a Faculty of Biosciences and Medical Engineering, Bioinformatics Research Group (BIRG), Biosciences & Health Sciences Department , Universiti Teknologi Malaysia , Skudai , Malaysia.
J Biomol Struct Dyn. 2015;33(11):2380-9. doi: 10.1080/07391102.2015.1036461. Epub 2015 Jun 8.
Systems metabolic engineering and in silico analyses are necessary to study gene knockout candidate for enhanced succinic acid production by Escherichia coli. Metabolically engineered E. coli has been reported to produce succinate from glucose and glycerol. However, investigation on in silico deletion of ptsG/b1101 gene in E. coli from glycerol using minimization of metabolic adjustment algorithm with the OptFlux software platform has not yet been elucidated. Herein we report what is to our knowledge the first direct predicted increase in succinate production following in silico deletion of the ptsG gene in E. coli GEM from glycerol with the OptFlux software platform. The result indicates that the deletion of this gene in E. coli GEM predicts increased succinate production that is 20% higher than the wild-type control model. Hence, the mutant model maintained a growth rate that is 77% of the wild-type parent model. It was established that knocking out of the ptsG/b1101 gene in E. coli using glucose as substrate enhanced succinate production, but the exact mechanism of this effect is still obscure. This study informs other studies that the deletion of ptsG/b1101 gene in E. coli GEM predicted increased succinate production, enabling a model-driven experimental inquiry and/or novel biological discovery on the underground metabolic role of this gene in E. coli central metabolism in relation to increasing succinate production when glycerol is the substrate.
系统代谢工程和计算机模拟分析对于研究大肠杆菌中增强琥珀酸生产的基因敲除候选基因是必要的。据报道,经过代谢工程改造的大肠杆菌可从葡萄糖和甘油中产生琥珀酸。然而,使用OptFlux软件平台的代谢调节最小化算法对大肠杆菌中甘油的ptsG/b1101基因进行计算机模拟缺失的研究尚未阐明。在此,我们报告据我们所知,使用OptFlux软件平台对大肠杆菌甘油代谢模型(E. coli GEM)中的ptsG基因进行计算机模拟缺失后,首次直接预测琥珀酸产量会增加。结果表明,在大肠杆菌甘油代谢模型中删除该基因可预测琥珀酸产量增加,比野生型对照模型高20%。因此,突变模型的生长速率维持在野生型亲本模型的77%。已确定以葡萄糖为底物敲除大肠杆菌中的ptsG/b1101基因可提高琥珀酸产量,但其确切机制仍不清楚。本研究为其他研究提供了信息,即大肠杆菌甘油代谢模型中ptsG/b1101基因的缺失预测琥珀酸产量会增加,从而能够进行模型驱动的实验探究和/或关于该基因在大肠杆菌中心代谢中与以甘油为底物时增加琥珀酸产量相关的地下代谢作用的新生物学发现。