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微生物菌株的稳健设计。

Robust design of microbial strains.

机构信息

Department of Mathematics and Computer Science, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.

出版信息

Bioinformatics. 2012 Dec 1;28(23):3097-104. doi: 10.1093/bioinformatics/bts590. Epub 2012 Oct 7.

Abstract

MOTIVATION

Metabolic engineering algorithms provide means to optimize a biological process leading to the improvement of a biotechnological interesting molecule. Therefore, it is important to understand how to act in a metabolic pathway in order to have the best results in terms of productions. In this work, we present a computational framework that searches for optimal and robust microbial strains that are able to produce target molecules. Our framework performs three tasks: it evaluates the parameter sensitivity of the microbial model, searches for the optimal genetic or fluxes design and finally calculates the robustness of the microbial strains. We are capable to combine the exploration of species, reactions, pathways and knockout parameter spaces with the Pareto-optimality principle.

RESULTS

Our framework provides also theoretical and practical guidelines for design automation. The statistical cross comparison of our new optimization procedures, performed with respect to currently widely used algorithms for bacteria (e.g. Escherichia coli) over different multiple functions, reveals good performances over a variety of biotechnological products.

AVAILABILITY

http://www.dmi.unict.it/nicosia/pathDesign.html.

CONTACT

nicosia@dmi.unict.it or pl219@cam.ac.uk

SUPPLEMENTARY INFORMATION

Supplementary data are available at Bioinformatics online.

摘要

动机

代谢工程算法提供了优化生物过程的手段,从而改善具有生物技术应用价值的分子。因此,了解如何在代谢途径中采取行动对于获得生产方面的最佳结果非常重要。在这项工作中,我们提出了一个计算框架,用于搜索能够生产目标分子的最佳和稳健的微生物菌株。我们的框架执行三项任务:评估微生物模型的参数敏感性,搜索最佳的遗传或通量设计,最后计算微生物菌株的稳健性。我们能够将物种、反应、途径和敲除参数空间的探索与 Pareto 最优原理相结合。

结果

我们的框架还为设计自动化提供了理论和实践指导。针对不同的多种功能,对我们的新优化程序与目前广泛用于细菌(例如大肠杆菌)的算法进行的统计交叉比较,揭示了在各种生物技术产品上的良好性能。

可用性

http://www.dmi.unict.it/nicosia/pathDesign.html。

联系人

nicosia@dmi.unict.itpl219@cam.ac.uk

补充信息

补充数据可在“Bioinformatics”在线获取。

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