The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark.
The Department of Biology & Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, United Kingdom; The Centre for Sustainable Chemical Technologies (CSCT), University of Bath, Claverton Down, Bath, BA2 7AY, United Kingdom.
Metab Eng. 2021 May;65:123-134. doi: 10.1016/j.ymben.2021.03.002. Epub 2021 Mar 19.
Parageobacillus thermoglucosidasius represents a thermophilic, facultative anaerobic bacterial chassis, with several desirable traits for metabolic engineering and industrial production. To further optimize strain productivity, a systems level understanding of its metabolism is needed, which can be facilitated by a genome-scale metabolic model. Here, we present p-thermo, the most complete, curated and validated genome-scale model (to date) of Parageobacillus thermoglucosidasius NCIMB 11955. It spans a total of 890 metabolites, 1175 reactions and 917 metabolic genes, forming an extensive knowledge base for P. thermoglucosidasius NCIMB 11955 metabolism. The model accurately predicts aerobic utilization of 22 carbon sources, and the predictive quality of internal fluxes was validated with previously published C-fluxomics data. In an application case, p-thermo was used to facilitate more in-depth analysis of reported metabolic engineering efforts, giving additional insight into fermentative metabolism. Finally, p-thermo was used to resolve a previously uncharacterised bottleneck in anaerobic metabolism, by identifying the minimal required supplemented nutrients (thiamin, biotin and iron(III)) needed to sustain anaerobic growth. This highlights the usefulness of p-thermo for guiding the generation of experimental hypotheses and for facilitating data-driven metabolic engineering, expanding the use of P. thermoglucosidasius as a high yield production platform.
耐热栖热菌代表了一种嗜热、兼性厌氧的细菌底盘，具有许多代谢工程和工业生产所需的理想特性。为了进一步优化菌株的生产力，需要对其代谢进行系统水平的了解，这可以通过基因组规模的代谢模型来实现。在这里，我们提出了 p-thermo，这是迄今为止最完整、经过精心整理和验证的 Parageobacillus thermoglucosidasius NCIMB 11955 基因组规模模型。它总共涵盖了 890 种代谢物、1175 种反应和 917 种代谢基因，为 Parageobacillus thermoglucosidasius NCIMB 11955 的代谢提供了广泛的知识库。该模型准确预测了需氧利用 22 种碳源的情况，并且内部通量的预测质量已经通过以前发表的 C-fluxomics 数据进行了验证。在一个应用案例中，p-thermo 被用于促进对已报道的代谢工程工作的更深入分析，从而对发酵代谢有了更多的了解。最后，p-thermo 被用于解决厌氧代谢中以前未被描述的瓶颈问题，确定了维持厌氧生长所需的最小补充营养物（硫胺素、生物素和三价铁）。这突出了 p-thermo 用于指导实验假设生成和促进数据驱动的代谢工程的有用性，扩大了耐热栖热菌作为高产生产平台的使用。
