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

梭状芽胞杆菌属是一组古老的细菌，在地球有氧气大气之前进化而来。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”。它们还具有产生孢子休眠阶段的能力，使它们能够在暴露于空气中存活。这些孢子对许多其他物理和化学物质也有抵抗力。有些物种会导致毁灭性的疾病。一些物种会导致毁灭性的疾病，例如超级细菌艰难梭菌。另一方面，大多数梭状芽孢杆菌都是完全良性的，它们从植物材料中生产各种化学物质的能力正在被工业界作为从原油中产生这些化学物质的替代方案。其中的主要例子是乙酰丁酸杆菌，这是一种在商业生产溶剂方面有着悠久历史的有机体，最著名的是‘丁醇’。丁醇是一种酒精，就像它的对手乙醇一样，它可以被用作汽油的替代品作为燃料。目前，乙醇作为汽油添加剂的使用在发达国家很普遍。如果我们要减少对有限原油资源的依赖，开发石油的替代品作为燃料是至关重要的。然而，丁醇具有许多性质，使其远远优于乙醇。它的能量含量高于乙醇，其低蒸气压力和对汽油混合物中水污染的耐受性有利于其在现有汽油供应和分销渠道中的使用。此外，丁醇可以以比现有生物燃料更高的浓度混合到汽油中，而不需要对汽车发动机进行昂贵的修改。与汽油-乙醇混合燃料相比，它还具有更好的燃油经济性。尽管它们很重要，但我们对梭状芽胞杆菌细胞生物学的了解一直落后于最近进化的“呼吸”氧气的细菌的数据。随着新世纪的到来，情况发生了变化。七种不同梭状芽胞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，这反映了它的商业重要性。这个项目的目的是对梭状芽孢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产生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被重新创建为一个反映活细胞的计算机程序。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综合学科(遗传学、转录组学、蛋白质组学、新陈代谢组学、生物化学、化学工程和数学模型)来实现。目前的研究方案将通过为所涉及的各种复杂生物过程开发多尺度数学模型，为这一更广泛的努力作出贡献。能够更有效地预测梭状芽胞杆菌的行为和代谢反应，将使乙酰丁酸梭菌能够更有效地用于丁醇的商业生产和作为抗癌载体。它还将使人们更好地了解致病物种的生物学，并最终开发出更有效的医学对策。

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.