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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.

梭状芽胞杆菌属是一种古老的细菌群，在地球有氧气环境之前就进化了。对它们来说，我们呼吸的空气中的氧气是一种毒药，因此它们被称为“厌氧菌”。它们的另一个特点是能够产生孢子休眠期，使它们能够暴露在空气中生存。这些孢子也能抵抗许多其他物理和化学药剂。有些物种会导致毁灭性的疾病。有些种类会导致毁灭性的疾病，比如超级细菌艰难梭菌。另一方面，大多数梭菌是完全良性的，它们从植物材料中生产各种化学物质的能力正被工业所追求，作为从原油中生产这些化学物质的替代品。其中最主要的是C. acetobutylicum，这种生物在溶剂的商业生产方面有着悠久的历史，最著名的是“丁醇”。丁醇是一种酒精，它和乙醇一样可以作为汽油的替代品。目前，乙醇作为汽油添加剂在发达国家广泛使用。如果我们要减少对有限的原油资源的依赖，开发石油替代品作为燃料是必不可少的。然而，丁醇的许多特性使它远远优于乙醇。它的能量含量比乙醇高，而且蒸气压低，汽油混合物耐水污染，便于在现有的汽油供应和分销渠道中使用。此外，与现有的生物燃料相比，丁醇可以以更高的浓度混合到汽油中，而无需对汽车发动机进行昂贵的改装。它也提供了比汽油-乙醇混合物更好的燃料经济性。尽管它们很重要，但我们对梭状芽胞杆菌的生物学理解仍落后于对新近进化的“呼吸”氧气的细菌的了解。随着新世纪的到来，情况发生了变化。7种不同梭状芽孢杆菌的完整遗传蓝图（基因组序列）现已确定。首先是乙酰丁酸梭菌，这反映了它在商业上的重要性。这个项目的目的是对这种梭状芽胞杆菌生长时发生的生物过程进行广泛的分析。特别是，我们希望了解在正常细胞生长和丁醇生产和孢子形成之间的过渡过程中发生的关键事件。我们的目的是建立一个这些过程的数学模型，这样这个过程就可以作为一个反映活细胞的计算机程序来重现。这些目标将通过一个由来自三个成员国（德国、荷兰和英国）的11名欧洲科学家组成的联盟部署的学科组合（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）来推进。目前的研究方案将通过为所涉及的各种复杂生物过程发展多尺度数学模型来促进这一更广泛的努力。更有效地预测梭菌的行为和代谢反应的能力将使C. acetobutylicum在丁醇的商业生产和抗癌运载工具中得到更有效的利用。它还将导致对致病物种的生物学有更深入的了解，并最终制定更有效的医疗对策。