Development and application of an in silico metabolic model of Geobacillus thermoglucosidasius

热葡萄糖苷酶计算机模拟代谢模型的建立及应用

• 批准号: BB/I015841/2
• 金额: $ 9.1万
• 依托单位: University of Bath
• 依托单位国家: 英国
• 项目类别: Training Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI015841%2F2
• 关键词: Development; application; silico; metabolic; model

TMO Renewables Ltd, the CASE collaborating company, has developed an ethanol fermentation process capable of using sugars derived from lignocellulosic substrates, based on engineering the fermentation pathways of Geobacillus thermoglucosidasius. As part of the work they have contracted to obtain the genome sequence of this organism, which is almost complete. In the initial stages, the annotation of a genome sequence is usually done automatically, based on the search for open reading frames (orfs) and bio-informatic homology searches. This means that initial annotations often contain errors and unclassified orfs. In this project the student will start to build a genomic scale metabolic model of this organism, using the initial genome sequence as a starting point. The ultimate goal is to build an in silico model of the metabolic capabilities of this organism based on Palsson's flux balance analysis approach (Palsson BO (2006) Systems Biology. Properties of Reconstructed Networks. Cambridge University Press, New York, USA). However, because Geobacillus spp are not extensively described at a biochemical and physiological level, this will require a considerable amount of experimental validation to eg confirm the gene assignments and fill in missing metabolic links. Once constructed, an in silico metabolic model can have predictive capabilities. Initially, these can be used to authenticate the quality of the model, which invariably includes an number of assumptions/estimates. However, in the long term, these may be used to predict the optimal route for metabolic engineering for a defined objective, which is one of the future aims of the company. In the interim, however, the logical iterative experimental and in silico construction of the model should generate new insights into the physiology and biochemistry of this increasingly important group of thermophiles. The combined experimental and modelling aspects of this programme will form an excellent training programme for a postgraduate student with a biological background, exposing them to one of the more accessible avenues of systems biology.

案例合作公司TMO Renewables Ltd开发了一种乙醇发酵过程，该过程能够使用源自木质纤维素底物衍生的糖，基于工程化的Geobacillus Thermogacillus thermogogosidasius的发酵途径。作为工作的一部分，他们签订了几乎完整的生物体的基因组序列。在初始阶段，基因组序列的注释通常是根据搜索开放式阅读框（ORF）和生物形式同源性搜索自动完成的。这意味着初始注释通常包含错误和未分类的ORF。在这个项目中，学生将使用初始基因组序列作为起点开始建立该生物体的基因组量表代谢模型。最终目标是基于Palsson的Flux平衡分析方法（Palsson Bo（2006）Systems Biology。重建网络的属性。剑桥大学出版社，纽约，美国，基于Palsson Flux平衡分析方法（Palsson Bo（2006），建立该生物的代谢能力的硅模型。但是，由于在生化和生理水平上未广泛描述地理菌SPP，因此这将需要大量的实验验证来确认基因分配并填充缺失的代谢环节。构造后，硅代谢模型可以具有预测能力。最初，这些可用于验证模型的质量，这些质量总是包含许多假设/估计值。但是，从长远来看，这些物品可用于预测定义目标的代谢工程的最佳途径，这是公司的未来目标之一。然而，在此期间，该模型的逻辑迭代实验和硅构建中应产生对这一日益重要的嗜热群体的生理和生物化学的新见解。该计划的结合实验和建模方面将为具有生物学背景的研究生提供出色的培训计划，将其暴露于系统生物学较容易获得的途径之一。