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

模拟枯草芽孢杆菌的碳核心代谢 - 探索蛋白质复合物在核心碳和氮代谢中的贡献

• 批准号: BB/I00470X/1
• 负责人: Hans Westerhoff
• 金额: $ 43.22万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI00470X%2F1
• 关键词: Modelling; carbon; core; metabolism; Bacillus

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.

灭火有两种方法。一个使用带有管道的水泵，填满一条通往火灾所在地的沟渠（“水池”），然后另一个水泵将水抽出，喷到火上。另一个是一排人，第一个人在附近的河里装满每个水桶，然后把装满的水桶交给下一个人，下一个人再把它交给下一个人，等等，即“水桶旅”机制。生物体如何从食物中提取能量和碳的化学过程是按照路径组织的。这种组织可以采用联营机制，也可以采用水桶队机制。在大多数关于这一主题的教科书中，都假设是池机制起作用，但这主要是因为这更容易理解，也更容易通过实验进行检验。因此，活细胞化学的数学模型倾向于假设池机制是可操作的。在这些途径中执行各个步骤/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，发现这些酶中的一些相互结合，即形成复合物。该提案旨在定义和理解代谢和调节多酶复合物对中心碳和氮代谢的影响。它将在枯草芽孢杆菌中做到这一点，枯草芽孢杆菌是系统生物学方法的一种高度易处理的模式生物。它将审查是否有任何观察到的影响是通过促进水桶旅机制（也称为代谢通道）。它将通过建模和实验的紧密结合来做到这一点。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。它也可能导致新的方法来干扰这种化学反应，例如通过破坏或促进酶-酶爱情事件。影响可能涉及利用微生物生产食品和化学品（啤酒、面包、葡萄酒、酒精汽油）和卫生管理领域，但需要开展后续项目。

项目成果

Targeting pathogen metabolism without collateral damage to the host.

• DOI: 10.1038/srep40406
• 发表时间: 2017-01-13
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Haanstra JR;Gerding A;Dolga AM;Sorgdrager FJH;Buist-Homan M;du Toit F;Faber KN;Holzhütter HG;Szöör B;Matthews KR;Snoep JL;Westerhoff HV;Bakker BM
• 通讯作者: Bakker BM

Systems biology of HIF metabolism in cancer

• 发表时间: 2012-10
• 期刊: Mutagenesis
• 影响因子: 2.7
• 作者: Emily G. Armitage;H. Westerhoff;Helen L. Kotze;R. Goodacre;N. Lockyer;K. Williams

(Im)Perfect robustness and adaptation of metabolic networks subject to metabolic and gene-expression regulation: marrying control engineering with metabolic control analysis.

• DOI: 10.1186/1752-0509-7-131
• 发表时间: 2013-11-21
• 期刊: BMC systems biology
• 作者: He F;Fromion V;Westerhoff HV
• 通讯作者: Westerhoff HV

Engineering of self-sustaining systems: Substituting the yeast glucose transporter plus hexokinase for the Lactococcus lactis phosphotransferase system in a Lactococcus lactis network in silico

• DOI: 10.1002/biot.201100314
• 发表时间: 2012-07-01
• 期刊: BIOTECHNOLOGY JOURNAL
• 影响因子: 4.7
• 作者: Adamczyk, Malgorzata;Westerhoff, Hans V.
• 通讯作者: Westerhoff, Hans V.

Systems biology of chemotherapy in hypoxia environments

• 发表时间: 2012-11
• 期刊: Mutagenesis
• 影响因子: 2.7
• 作者: Helen L. Kotze;H. Westerhoff;N. Lockyer;R. Goodacre;Emily G. Armitage;K. Williams