SysMO: Systems Biology of Clostridium acetobutylicum - a possible answer to dwindling crude oil reserves.

SysMO：丙酮丁醇梭菌的系统生物学 - 原油储量减少的可能答案。

基本信息

批准号：
BB/F003382/1
负责人：
John King
金额：
$ 33.17万
依托单位：
University of Nottingham
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2007
资助国家：
英国
起止时间：
2007 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FF003382%2F1
关键词：
SysMO Systems Biology Clostridium acetobutylicum

项目摘要

The genus Clostridium are an ancient grouping of bacteria which evolved before the earth had an oxygen atmosphere. To them oxygen in the air we breathe is a poison, and they are therefore called 'anaerobes'. They are also characterised by an ability to produce a spore resting stage that enables them to survive exposure to the air. These spores are also resistant to many other physical and chemical agents. Some species cause devastating diseases. Some species cause devastating diseases, such as the superbug Clostridium difficile. On the other hand, most clostridia are entirely benign, and their ability to produce a wide range of diverse chemicals from plant material is being pursued by industry as an alternative to generating these chemicals from crude oil. Principle amongst these is C. acetobutylicum, an organism with a longstanding history in the commercial production of solvents, most notably 'butanol'. Butanol is an alcohol, which, like its counterpart ethanol may be used as a replacement for petrol as a fuel. Currently, the use of ethanol as a petrol additive is widespread in the developed world. The development of alternatives to petroleum as fuels is essential if we are to reduce our reliance on finite crude oil resources. However, butanol has many properties that make it far superior to ethanol. It has a higher energy content than ethanol, and its low vapour pressure and its tolerance to water contamination in petrol blends facilitate its use in existing petrol supply and distribution channels. Moreover, butanol can be blended into petrol at higher concentrations than existing biofuels, without the need to make expensive modifications to car engines. It also gives better fuel economy than petrol-ethanol blends. Despite their importance, our understanding of the biology of the Clostridium cell has lagged behind the data available for more recently evolved bacteria which 'breathe' oxygen. With the dawn of a new century the situation has changed. The complete genetic blueprint (genome sequence) of seven different Clostridium species has now been determined. The first was that of Clostridium acetobutylicum, a reflection of its commercial importance. It is the intention of this project to undertake an extensive analysis of the biological processes that take place when this Clostridium grows. In particular, we wish to understand the key events that occur during the transition between normal cell growth and the onset of both butanol production and spore formation. Our intention is to build a mathematical model of these processes such that the process may be recreated as a computer programme that mirrors the living cell. These aims will be progressed through a combination of disciplines (genetics, transcriptomics, proteomics, metabolomics, biochemistry, chemical engineering and mathematical modelling) deployed by a consortium of eleven European scientists, from three member states (Germany, the Netherlands and the UK). The current research programme will contribute to this broader effort by developing multiscale mathematical models for the various complex biological processes involved. The ability to predict more effectively the behavioural and metabolic response of clostridia will enable the more effective exploitation of C. acetobutylicum in the commercial production of butanol and as an anti-cancer delivery vehicle. It will also lead to a greater understanding of the biology of pathogenic species and, ultimately, to the development of more effective medical countermeasures.

梭状芽胞杆菌是古老的细菌分组，在地球具有氧气气氛之前进化。在空中，我们呼吸的氧气是一种毒药，因此被称为“厌氧”。它们的特征还具有产生孢子休息阶段的能力，使它们能够生存在空气中。这些孢子也对许多其他物理和化学剂具有抵抗力。一些物种会引起毁灭性疾病。一些物种会导致毁灭性疾病，例如艰难梭菌的超级梭菌。另一方面，大多数梭状芽胞杆菌都是完全良性的，工业正在追求它们从植物材料中产生各种不同化学物质的能力，作为从原油中产生这些化学物质的替代方法。其中的原理是乙酸梭菌（C. actobutlicum），这是一种在溶剂的商业生产中具有悠久历史的生物，最著名的是“丁醇”。丁醇是一种酒精，就像其对应物乙醇一样，可以用作替代汽油作为燃料。目前，将乙醇用作汽油添加剂在发达国家广泛。如果我们要减少对有限的原油资源的依赖，则必须开发石油作为燃料。但是，丁醇具有许多使其优于乙醇的特性。它的能量含量高于乙醇，其低蒸气压力及其对汽油混合物中水污染的耐受性有助于其在现有的汽油供应和分配通道中的使用。此外，与现有生物燃料相比，丁醇可以以高浓度将其混合成汽油，而无需对汽车发动机进行昂贵的修改。它还比汽油 - 乙醇混合物可以提供更好的燃油经济性。尽管它们的重要性，但我们对梭状芽孢杆菌细胞生物学的理解却落后于最近进化的细菌可用的数据，这些细菌“呼吸”了氧。随着新世纪的曙光，情况发生了变化。现在已经确定了七个不同的梭状芽胞杆菌物种的完整遗传蓝图（基因组序列）。首先是乙梭状芽孢杆菌的商业意义。该项目的目的是对梭状芽孢杆菌生长时发生的生物学过程进行广泛的分析。特别是，我们希望了解正常细胞生长与丁醇产生和孢子形成之间过渡期间发生的关键事件。我们的目的是构建这些过程的数学模型，以便可以将过程重新创建为反映活细胞的计算机程序。这些目标将通过学科（遗传学，转录组学，蛋白质组学，代谢组学，生物化学，化学工程和数学建模）的结合来实现，该联盟由十一个欧洲科学家的联盟部署，来自三个成员国（德国，荷兰和英国）。当前的研究计划将通过为所涉及的各种复杂的生物过程开发多尺度数学模型来为这一更广泛的努力做出贡献。更有效地预测梭菌的行为和代谢反应的能力将使在商业生产中对丁醇和作为抗癌递送工具进行更有效的利用。这也将使人们对致病物种的生物学有更深入的了解，并最终导致更有效的医学对策的发展。