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.

TMO可再生能源有限公司是CASE的合作公司，已经开发出一种乙醇发酵工艺，能够使用从木质纤维素基质中提取的糖，该工艺基于热葡萄球菌发酵途径的工程设计。作为工作的一部分，他们已经签约获得这种生物体的基因组序列，这几乎是完整的。在初始阶段，基因组序列的注释通常是自动完成的，基于开放阅读框（orfs）搜索和生物信息学同源性搜索。这意味着最初的注释通常包含错误和未分类的注释。在本项目中，学生将以初始基因组序列为起点，开始构建该生物的基因组尺度代谢模型。最终目标是基于Palsson的通量平衡分析方法（Palsson BO (2006) Systems Biology）建立该生物代谢能力的计算机模型。重构网络的性质。剑桥大学出版社，美国纽约)。然而，由于地杆菌没有在生化和生理水平上得到广泛的描述，这将需要大量的实验验证，例如确认基因分配并填补缺失的代谢环节。一旦构建，计算机代谢模型就可以具有预测能力。最初，这些可以用来验证模型的质量，模型总是包含许多假设/估计。然而，从长远来看，这些可以用来预测代谢工程的最佳路线，以实现一个确定的目标，这是该公司未来的目标之一。然而，在此期间，该模型的逻辑迭代实验和计算机构建应该会对这一日益重要的嗜热菌群体的生理和生物化学产生新的见解。本课程的实验和建模方面的结合将为具有生物学背景的研究生提供一个优秀的培训计划，使他们接触到系统生物学更容易接近的途径之一。