结合计算机模拟和体外实验方法研究甲基赤藓醇 4-磷酸和莽草酸途径在根癌农杆菌中增强辅酶 Q10 产量的作用。

Combining in silico and in vitro approaches to understand the involvement of methylerythritol 4-phosphate and shikimate pathways in Agrobacterium tumefaciens for enhanced coenzyme Q10 production.

机构信息

Department of Biotechnology, Central University of Haryana, Jant-Pali, Mahendergarh 123031, India.

Bioinformatics Core, Purdue University, West Lafayette, Indiana, USA-47907, USA.

出版信息

J Appl Microbiol. 2023 May 2;134(5). doi: 10.1093/jambio/lxad097.

DOI:10.1093/jambio/lxad097

PMID:37160352

Abstract

AIMS

To perform an integrated comparative analysis of metabolic pathway to understand coenzyme Q10 (CoQ10) production in Agrobacterium tumefaciens.

METHODS AND RESULTS

Comparative analysis of the CoQ10 metabolic pathway in 10 organisms using a genome to KEGG orthology program (G2KO) and the KEGG database elucidated the completeness of the production pathway in A. tumefaciens. The specific roles of the key precursors and the enzymes in the metabolic network were subsequently confirmed using pathway inhibitors and enhancers. While the use of fosmidomycin and glyphosate was found to inhibit CoQ10 production by 54.54% to 99%, the supplementation of polyprenyl pyrophosphate of the methylerythritol 4-phosphate pathway and 4-hydroxybenzoate precursor of the shikimate pathway did increse the production of CoQ10 by 2.3-fold.

CONCLUSIONS

The present study provides a comprehensive understanding of the CoQ10 biosynthetic pathway in A. tumefaciens, which would assist rational metabolic engineering strategies for augmenting CoQ10 biosynthesis.

摘要

目的

对代谢途径进行综合比较分析，以了解农杆菌中辅酶 Q10（CoQ10）的生产。

方法与结果

使用基因组到 KEGG 直系同源物程序（G2KO）和 KEGG 数据库对 10 种生物的 CoQ10 代谢途径进行比较分析，阐明了农杆菌中生产途径的完整性。随后使用途径抑制剂和增强剂来确定代谢网络中关键前体和酶的具体作用。虽然发现使用福斯霉素和草甘膦可使 CoQ10 的产量抑制 54.54%至 99%，但补充甲基赤藓醇 4-磷酸途径的多聚异戊烯焦磷酸和莽草酸途径的 4-羟基苯甲酸前体可使 CoQ10 的产量增加 2.3 倍。