Namrak Thanawat, Raethong Nachon, Jatuponwiphat Theeraphol, Nitisinprasert Sunee, Vongsangnak Wanwipa, Nakphaichit Massalin
Specialized Research Unit: Prebiotics and Probiotics for Health, Department of Biotechnology, Faculty of Agro-Industry, Kasetsart University, Bangkok 10900, Thailand.
Institute of Nutrition, Mahidol University, Nakhon Pathom 73170, Thailand.
Biology (Basel). 2022 Feb 11;11(2):294. doi: 10.3390/biology11020294.
KUB-AC5 displays the hallmark features of probiotic properties for food and feed industries. Optimization of cultivation condition for the industrial production is important to reach cell concentration and cost reduction. Considering the strain-specific growth physiology, metabolic capability, and essential nutrients of KUB-AC5, the genome-scale metabolic model (GSMM) of KUB-AC5 was developed. Hereby, the GSMM of TN656 was successfully constructed which contained 656 genes, 831 metabolites, and 953 metabolic reactions. The TN656 model could show a metabolic capability under various carbon sources and guide potentially 14 essential single nutrients (e.g., vitamin B complex and amino acids) and 2 essential double nutrients (pairwise glutamine-glutamate and asparagine-aspartate) for KUB-AC5 growth through single and double omission analysis. Promisingly, the TN656 model was further integrated with transcriptome data suggesting that putative metabolic routes as preferable paths e.g., sucrose uptake, nucleotide biosynthesis, urea cycle, and glutamine transporter for KUB-AC5 growth. The developed GSMM offers a powerful tool for multi-level omics analysis, enabling probiotic strain optimization for biomass overproduction on an industrial scale.
KUB-AC5展现出了适用于食品和饲料行业的益生菌特性的标志性特征。优化工业生产的培养条件对于提高细胞浓度和降低成本至关重要。考虑到KUB-AC5的菌株特异性生长生理学、代谢能力和必需营养物质，构建了KUB-AC5的基因组规模代谢模型（GSMM）。据此，成功构建了包含656个基因、831种代谢物和953个代谢反应的TN656的GSMM。TN656模型可以显示在各种碳源下的代谢能力，并通过单因素和双因素缺失分析指导KUB-AC5生长所需的潜在14种必需单一营养物质（如复合维生素B和氨基酸）和2种必需双营养物质（谷氨酰胺-谷氨酸和天冬酰胺-天冬氨酸对）。有前景的是，TN656模型进一步与转录组数据整合，表明推定的代谢途径是KUB-AC5生长的优选途径，例如蔗糖摄取、核苷酸生物合成、尿素循环和谷氨酰胺转运体。所构建的GSMM为多层次组学分析提供了一个强大的工具，能够在工业规模上对益生菌菌株进行优化以实现生物量的过量生产。
