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代谢的计算机模拟工程揭示了提高生物表面活性剂产量的新生物标志物。

In silico engineering of metabolism reveals new biomarkers for increased biosurfactant production.

作者信息

Occhipinti Annalisa, Eyassu Filmon, Rahman Thahira J, Rahman Pattanathu K S M, Angione Claudio

机构信息

Department of Computer Science and Information Systems, Teesside University, Middlesbrough, UK.

Technology Futures Institute, School of Science, Engineering and Design, Teesside University, Middlesbrough, UK.

出版信息

PeerJ. 2018 Dec 17;6:e6046. doi: 10.7717/peerj.6046. eCollection 2018.

Abstract

BACKGROUND

Rhamnolipids, biosurfactants with a wide range of biomedical applications, are amphiphilic molecules produced on the surfaces of or excreted extracellularly by bacteria including . However, is a non-pathogenic model organism with greater metabolic versatility and potential for industrial applications.

METHODS

We investigate in silico the metabolic capabilities of for rhamnolipids biosynthesis using statistical, metabolic and synthetic engineering approaches after introducing key genes ( and ) from into a genome-scale model of . This pipeline combines machine learning methods with multi-omic modelling, and drives the engineered model toward an optimal production and export of rhamnolipids out of the membrane.

RESULTS

We identify a substantial increase in synthesis of rhamnolipids by the engineered model compared to the control model. We apply statistical and machine learning techniques on the metabolic reaction rates to identify distinct features on the structure of the variables and individual components driving the variation of growth and rhamnolipids production. We finally provide a computational framework for integrating multi-omics data and identifying latent pathways and genes for the production of rhamnolipids in .

CONCLUSIONS

We anticipate that our results will provide a versatile methodology for integrating multi-omics data for topological and functional analysis of toward maximization of biosurfactant production.

摘要

背景

鼠李糖脂是一类具有广泛生物医学应用的生物表面活性剂,是包括[细菌名称]在内的细菌在表面产生或细胞外分泌的两亲性分子。然而,[细菌名称]是一种具有更高代谢多样性和工业应用潜力的非致病模式生物。

方法

在将来自[细菌名称]的关键基因([基因名称1]和[基因名称2])引入[目标细菌名称]的基因组规模模型后,我们使用统计、代谢和合成工程方法在计算机上研究[目标细菌名称]合成鼠李糖脂的代谢能力。该流程将机器学习方法与多组学建模相结合,并驱动工程化的[目标细菌名称]模型实现鼠李糖脂在膜外的最优生产和输出。

结果

我们发现与对照模型相比,工程化模型合成的鼠李糖脂大幅增加。我们对代谢反应速率应用统计和机器学习技术,以识别驱动生长和鼠李糖脂生产变化的变量和单个组分结构上的独特特征。我们最终提供了一个计算框架,用于整合多组学数据并识别[目标细菌名称]中生产鼠李糖脂的潜在途径和基因。

结论

我们预计我们的结果将提供一种通用方法,用于整合多组学数据以对[目标细菌名称]进行拓扑和功能分析,从而实现生物表面活性剂产量的最大化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757f/6301282/1b3cdc683463/peerj-06-6046-g001.jpg

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