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ERA-IB 5 ECOYEAST_rjb Mastering the economics of adaptation through constraint-based modeling in yeast

ERA-IB 5 ECOYEAST_rjb 通过酵母中基于约束的建模掌握适应经济学

基本信息

批准号：
BB/M025756/1
负责人：
Robert Beynon
金额：
$ 48.88万
依托单位：
University of Liverpool
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2015
资助国家：
英国
起止时间：
2015 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FM025756%2F1
关键词：
ERA IB ECOYEAST_rjb Mastering economics

项目摘要

Living cells evolved a remarkable ability to adapt to environmental conditions, or to withstand mutations. In biotechnology, this compromises success in metabolic engineering and causes instability of engineered strains. "Functional genomics" has allowed the cost-effective measurement of many of the components of the cell. However, we still mostly fail to understand how their interactions lead to cellular function and adaptation. It becomes clear, however, that physics and (bio)chemistry impose strong constraints on adaptation and evolution. Such constraints limit the total amount of protein that a cell can synthesize, and impact on how it should partition that limited resource over its processes to optimize fitness ("cellular economics"). Such knowledge is important to come with better metabolic engineering strategies that take into account the impact of novel genes and pathways on cellular economics, to develop processes with high yields that enable cost-effective bio-based chemicals and biofuels. In this proposal we will develop a modeling framework that will allow the integration of large data sets into comprehensive mechanistic models. These models are of genome-scale and will be able to compute the costs and benefits of implementing metabolic engineering strategies. The economic models will be used to provide proof-of-concept in two ways: (i) as tools for data integration and interpretation of adaptive responses; (ii) as predictive tool, through optimisation to predict more realistic theoretical yields and through exploration of metabolic engineering scenarios. This will be tested by a user case provided by our industrial partners, DSM and Roquette, involving succinate production, a versatile C4 diacid with a lot of potential applications, e.g. in polymers and resins.

活细胞进化出了适应环境条件或抵御突变的非凡能力。在生物技术中，这损害了代谢工程的成功，并导致工程菌株的不稳定性。“功能基因组学”允许对细胞的许多组分进行成本有效的测量。然而，我们仍然无法理解它们的相互作用如何导致细胞功能和适应。然而，很明显，物理学和（生物）化学对适应和进化施加了强大的限制。这些限制限制了细胞可以合成的蛋白质总量，并影响了它应该如何在其过程中分配有限的资源以优化适应性（“细胞经济学”）。这些知识对于制定更好的代谢工程策略非常重要，这些策略考虑到新基因和途径对细胞经济学的影响，以开发具有高产量的过程，从而实现具有成本效益的生物基化学品和生物燃料。在本提案中，我们将开发一个建模框架，该框架将允许将大型数据集集成到全面的机械模型中。这些模型是基因组规模的，将能够计算实施代谢工程策略的成本和收益。经济模型将用于以两种方式提供概念验证：（i）作为数据整合和解释适应性反应的工具;（ii）作为预测工具，通过优化预测更现实的理论产量，并通过探索代谢工程方案。这将通过我们的工业合作伙伴帝斯曼（DSM）和罗盖特（Roquette）提供的用户案例进行测试，该案例涉及琥珀酸生产，琥珀酸是一种多用途的C4二元酸，具有许多潜在应用，例如在聚合物和树脂中。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

PEPPI-MS: Strategies to Enhance the Extraction of Electrophoretically Separated Proteins from Polyacrylamide Gels and Their Application to Top-Down/native Mass Spectrometry

PEPPI-MS：增强从聚丙烯酰胺凝胶中提取电泳分离蛋白质的策略及其在自上而下/天然质谱中的应用

DOI：
10.26434/chemrxiv.9917225.v1
发表时间：
2019
期刊：
影响因子：
0
作者：
Takemori A
通讯作者：
Takemori A

Whole-cell modeling in yeast predicts compartment-specific proteome constraints that drive metabolic strategies

酵母的全细胞建模预测了驱动代谢策略的区室特异性蛋白质组限制

DOI：
10.1101/2021.06.11.448029
发表时间：
2021
期刊：
影响因子：
0
作者：
Elsemman I
通讯作者：
Elsemman I

Whole-cell modeling in yeast predicts compartment-specific proteome constraints that drive metabolic strategies.

酵母中的全细胞建模可以预测驱动代谢策略的特定于隔室的蛋白质组约束。

DOI：
10.1038/s41467-022-28467-6
发表时间：
2022-02-10
期刊：
Nature communications
影响因子：
16.6
作者：
Elsemman IE;Rodriguez Prado A;Grigaitis P;Garcia Albornoz M;Harman V;Holman SW;van Heerden J;Bruggeman FJ;Bisschops MMM;Sonnenschein N;Hubbard S;Beynon R;Daran-Lapujade P;Nielsen J;Teusink B
通讯作者：
Teusink B

Mass spectrometry for structural analysis and quantification of the Major Urinary Proteins of the house mouse

DOI：
10.1016/j.ijms.2015.07.026
发表时间：
2015-11-30
期刊：
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
影响因子：
1.8
作者：
Beynon, Robert J.;Armstrong, Stuart D.;Woolerton, Yvonne E.
通讯作者：
Woolerton, Yvonne E.

PEPPI-MS: Polyacrylamide-Gel-Based Prefractionation for Analysis of Intact Proteoforms and Protein Complexes by Mass Spectrometry.

DOI：
10.1021/acs.jproteome.0c00303
发表时间：
2020-09-04
期刊：
Journal of proteome research
影响因子：
4.4
作者：
Takemori A;Butcher DS;Harman VM;Brownridge P;Shima K;Higo D;Ishizaki J;Hasegawa H;Suzuki J;Yamashita M;Loo JA;Loo RRO;Beynon RJ;Anderson LC;Takemori N
通讯作者：
Takemori N