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J1074全基因组规模代谢模型的重建:天然产物合成中改进的工程策略

Reconstruction of a Genome-Scale Metabolic Model of J1074: Improved Engineering Strategies in Natural Product Synthesis.

作者信息

Kittikunapong Cheewin, Ye Suhui, Magadán-Corpas Patricia, Pérez-Valero Álvaro, Villar Claudio J, Lombó Felipe, Kerkhoven Eduard J

机构信息

Department of Biology and Biological Engineering, Chalmers University of Technology, 41296 Gothenburg, Sweden.

Department of Functional Biology, IUOPA (Instituto Universitario de Oncología del Principado de Asturias) and ISPA (Instituto de Investigación Sanitaria del Principado de Asturias), University of Oviedo, 33006 Oviedo, Spain.

出版信息

Metabolites. 2021 May 11;11(5):304. doi: 10.3390/metabo11050304.

DOI:10.3390/metabo11050304
PMID:34064751
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8150979/
Abstract

J1074 is recognized as an effective host for heterologous production of natural products. Its fast growth and efficient genetic toolbox due to a naturally minimized genome have contributed towards its advantage in expressing biosynthetic pathways for a diverse repertoire of products such as antibiotics and flavonoids. In order to develop precise model-driven engineering strategies for de novo production of natural products, a genome-scale metabolic model (GEM) was reconstructed for the microorganism based on protein homology to model species   while drawing annotated data from databases and literature for further curation. To demonstrate its capabilities, the -GEM was used to predict overexpression targets for desirable compounds using flux scanning with enforced objective function (FSEOF). -GEM was also utilized to investigate the effect of a minimized genome on metabolic gene essentialities in comparison to another species, .

摘要

J1074被认为是异源生产天然产物的有效宿主。由于其天然最小化的基因组,它生长迅速且拥有高效的遗传工具包,这使其在表达多种产物(如抗生素和类黄酮)的生物合成途径方面具有优势。为了开发用于天然产物从头生产的精确模型驱动工程策略,基于与模式物种的蛋白质同源性,为该微生物重建了一个基因组规模的代谢模型(GEM),同时从数据库和文献中提取注释数据以进行进一步整理。为了证明其能力,使用具有强制目标函数的通量扫描(FSEOF),利用该GEM预测所需化合物的过表达靶点。与另一个物种相比,该GEM还被用于研究最小化基因组对代谢基因必需性的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b482/8150979/0c940cb42b47/metabolites-11-00304-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b482/8150979/8c9e6fc19499/metabolites-11-00304-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b482/8150979/4171007905c9/metabolites-11-00304-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b482/8150979/0c940cb42b47/metabolites-11-00304-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b482/8150979/8c9e6fc19499/metabolites-11-00304-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b482/8150979/4171007905c9/metabolites-11-00304-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b482/8150979/0c940cb42b47/metabolites-11-00304-g003.jpg

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