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一个33047的基因组规模代谢模型,用于指导基因改造以过量生产尼龙单体。

A Genome-Scale Metabolic Model of 33047 to Guide Genetic Modifications to Overproduce Nylon Monomers.

作者信息

Hendry John I, Dinh Hoang V, Sarkar Debolina, Wang Lin, Bandyopadhyay Anindita, Pakrasi Himadri B, Maranas Costas D

机构信息

Department of Chemical Engineering, The Pennsylvania State University, University Park, State College, PA 16802, USA.

Department of Biology, Washington University, St. Louis, MO 63130, USA.

出版信息

Metabolites. 2021 Mar 15;11(3):168. doi: 10.3390/metabo11030168.

Abstract

Nitrogen fixing-cyanobacteria can significantly improve the economic feasibility of cyanobacterial production processes by eliminating the requirement for reduced nitrogen. sp. ATCC 33047 is a marine, heterocyst forming, nitrogen fixing cyanobacteria with a very short doubling time of 3.8 h. We developed a comprehensive genome-scale metabolic (GSM) model, AnC892, for this organism using annotations and content obtained from multiple databases. AnC892 describes both the vegetative and heterocyst cell types found in the filaments of sp. ATCC 33047. AnC892 includes 953 unique reactions and accounts for the annotation of 892 genes. Comparison of AnC892 reaction content with the GSM of sp. PCC 7120 revealed that there are 109 reactions including uptake hydrogenase, pyruvate decarboxylase, and pyruvate-formate lyase unique to AnC892. AnC892 enabled the analysis of energy production pathways in the heterocyst by allowing the cell specific deactivation of light dependent electron transport chain and glucose-6-phosphate metabolizing pathways. The analysis revealed the importance of light dependent electron transport in generating ATP and NADPH at the required ratio for optimal N fixation. When used alongside the strain design algorithm, OptForce, AnC892 recapitulated several of the experimentally successful genetic intervention strategies that over produced valerolactam and caprolactam precursors.

摘要

固氮蓝藻可以通过消除对还原态氮的需求,显著提高蓝藻生产过程的经济可行性。sp. ATCC 33047是一种海洋、形成异形胞的固氮蓝藻,其倍增时间非常短,仅为3.8小时。我们利用从多个数据库获得的注释和内容,为这种生物开发了一个全面的基因组规模代谢(GSM)模型AnC892。AnC892描述了在sp. ATCC 33047丝状体中发现的营养细胞和异形胞细胞类型。AnC892包括953个独特反应,并对892个基因进行了注释。将AnC892的反应内容与sp. PCC 7120的GSM进行比较,发现有109个反应是AnC892独有的,包括摄取氢化酶、丙酮酸脱羧酶和丙酮酸甲酸裂解酶。通过允许细胞特异性失活光依赖电子传递链和6-磷酸葡萄糖代谢途径,AnC892能够分析异形胞中的能量产生途径。分析揭示了光依赖电子传递在以最佳固氮所需比例生成ATP和NADPH方面的重要性。当与菌株设计算法OptForce一起使用时,AnC892概括了几种实验成功的遗传干预策略,这些策略过量生产了戊内酰胺和己内酰胺前体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7331/7999273/0b158113ecf9/metabolites-11-00168-g001.jpg

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