Modelling carbon core metabolism in Bacillus subtilis - Exploring the contribution of protein complexes in core carbon and nitrogen metabolism

火可以用两种方法扑灭。一种是用带管子的水泵填满通往火源的沟渠（“水池”），然后另一种水泵把水抽出来喷到火上。另一种是一排人，第一个人把附近河里的桶装满，然后把装满的桶递给排在后面的人，然后再递给下一个人，以此类推，即“水桶队”机制。生物体从食物中提取能量和碳的化学过程是按照途径组织的。该组织可以使用池机制或桶大队机制。在大多数关于这个主题的教科书中，都假设是池机制在起作用，但这主要是因为这更容易理解，也更容易通过实验来检验。因此，活细胞化学的数学模型倾向于假设池机制是有效的。在这些途径中执行单个步骤/化学反应的生物“机器”被称为酶。在最近对一种重要细菌的研究中，人们发现这些酶中的一些相互结合，即形成复合物。本提案旨在定义和理解代谢和调节多酶复合物对中心碳氮代谢的影响。它将在枯草芽孢杆菌中做到这一点，这是一种高度可处理的模式生物，用于系统生物学方法。它将检查是否有任何观察到的影响是通过促进bucket-brigade机制（也称为代谢通道）。它将通过建模和实验的紧密结合来实现这一目标。这个项目的结果可能会极大地改变我们对生命化学的理解。它还可能导致干扰这种化学反应的新方法，例如，通过破坏或促进酶-酶恋爱。影响可能涉及微生物生产食品和化学品（啤酒、面包、葡萄酒、汽油）和健康管理等领域，但需要开展后续项目。

Fires can be extinguished in two ways. One uses pumps with pipes that fill up a ditch (the 'pool') that leads to where the fire is, and then another pump taking out the water squirting it onto the fire. The other one is a line of people where the first fills each bucket in a nearby river and then hands the full bucket to the person next in line, who hands it to the next-next, etcetera, i.e. the 'bucket-brigade' mechanism. The chemistry of how living organisms extract energy and carbon out of their food is organized in terms of pathways. This organization could use either the pool mechanism or the bucket brigade mechanism. In most of the text books on this topic it is assumed that it is the pool mechanism that operates, but this is mainly because this is simpler to understand and more readily examined experimentally. Accordingly, mathematical models of the chemistry of living cells tend to assume that pool mechanisms are operative. The biological 'machines' that carry out the individual steps/chemical reactions in the pathways are called enzymes. In recent work in an important bacterium, it has been discovered that some of these enzymes embrace each other, i.e. form complexes. This proposal aims at defining and understanding the impact of metabolic and regulatory multienzyme complexes on the central carbon and nitrogen metabolism. It will do this in Bacillus subtilis, a highly tractable model organism for systems biology approaches. It will examine whether any observed impact is through the facilitation of the bucket-brigade mechanism (also called metabolic channelling). It will do this through a close integration of modelling and experimentation. The outcome of this project could greatly change our understanding of the chemistry of Life. It could also lead to new ways of interfering with that chemistry, for instance by breaking up or promoting the enzyme-enzyme love affairs. Implications could be in the domains of the production of food and chemicals by microorganisms (beer, bread, wine, gasohol) and health management, but would require follow-up projects.