Pereira Bruno, Miguel Joana, Vilaça Paulo, Soares Simão, Rocha Isabel, Carneiro Sónia
SilicoLife Lda, Rua do Canastreiro 15, 4715-387, Braga, Portugal.
CEB - Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.
BMC Syst Biol. 2018 May 30;12(1):61. doi: 10.1186/s12918-018-0585-7.
Actinobacillus succinogenes is a promising bacterial catalyst for the bioproduction of succinic acid from low-cost raw materials. In this work, a genome-scale metabolic model was reconstructed and used to assess the metabolic capabilities of this microorganism under producing conditions.
The model, iBP722, was reconstructed based on the functional reannotation of the complete genome sequence of A. succinogenes 130Z and manual inspection of metabolic pathways, covering 1072 enzymatic reactions associated with 722 metabolic genes that involve 713 metabolites. The highly curated model was effective in capturing the growth of A. succinogenes on various carbon sources, as well as the SA production under various growth conditions with fair agreement between experimental and predicted data. Calculated flux distributions under different conditions show that a number of metabolic pathways are affected by the activity of some metabolic enzymes at key nodes in metabolism, including the transport mechanism of carbon sources and the ability to fix carbon dioxide.
The established genome-scale metabolic model can be used for model-driven strain design and medium alteration to improve succinic acid yields.
产琥珀酸放线杆菌是一种利用低成本原料生物生产琥珀酸的有前景的细菌催化剂。在本研究中,构建了一个基因组规模的代谢模型,并用于评估该微生物在生产条件下的代谢能力。
基于产琥珀酸放线杆菌130Z完整基因组序列的功能重新注释和代谢途径的人工检查,构建了模型iBP722,其涵盖了与722个代谢基因相关的1072个酶促反应,涉及713种代谢物。这个经过高度整理的模型能够有效地反映产琥珀酸放线杆菌在各种碳源上的生长情况,以及在各种生长条件下琥珀酸的生产情况,实验数据和预测数据之间具有较好的一致性。不同条件下计算得到的通量分布表明,一些代谢途径受到代谢关键节点处某些代谢酶活性的影响,包括碳源的转运机制和固定二氧化碳的能力。
所建立的基因组规模代谢模型可用于模型驱动的菌株设计和培养基改良,以提高琥珀酸产量。