动物双歧杆菌乳亚种BLa80基因组代谢网络模型的构建与验证

Construction and verification of a genome-scale metabolic model for Bifidobacterium animalis subsp. lactis BLa80

摘要:

随着基因测序技术的发展，基因组规模代谢网络模型作为一种能够系统性解析微生物代谢网络的工具愈发受到关注。本研究通过半自动建模方法构建了动物双歧杆菌乳亚种(Bifidobacterium animalis subsp. lactis) BLa80的基因组规模代谢模型并进行验证，以期为后续BLa80的代谢机制研究与益生功能解析提供便利工具。在模型结构质量方面，模型的代谢模型测试套件(the genome-scale metabolic model test suite, Memote)评分达到82%；在实验验证过程中，模型模拟出的B. lactis BLa80利用15种单一碳源生长的能力以及其需求的20种氨基酸与实验验证结果完全一致，基于已有合成培养基和改良MRS培养基模拟所得最大比生长速率以及对应的2种主要有机酸比合成速率与实验验证结果相比误差分别在5%及10%以内。最终建立的模型iMJ519包含1 005个反应、1 047种代谢物以及519个基因。本研究为深入研究B. lactis BLa80生长和代谢调控提供了有力工具。

Abstract:

With the advance of gene sequencing technology, genome-scale metabolic models have become favored tools for systematically analyzing microbial metabolic networks. In this study, a genome-scale metabolic model of Bifidobacterium animalis subsp. lactis BLa80 was constructed via a semi-automated modeling approach and subsequently validated, providing a tool for subsequent research into its metabolic mechanisms and probiotic functions. In terms of structural quality, the model achieved a Memote score of 82%. For wet-lab validation, the model’s simulations of growth on fourteen single carbon sources and amino acid requirements were fully consistent with experimental findings. The maximum specific growth rate and the corresponding specific production rates of two major organic acids predicted by the model based on the existing synthetic medium and modified MRS medium showed errors within 5% and 10%, respectively, compared to the experimental results. The final model, designated iMJ519, comprises 1 005 reactions, 1 047 metabolites, and 519 genes, providing a powerful tool for in-depth research on the growth and metabolic regulation of B. lactis BLa80.