文献类型：期刊文献

中文题名：分枝杆菌转化甾醇过程的中心代谢关键基因转录差异分析

英文题名：Transcription Variations of Key Genes in the Central Metabolism Pathways of the Sterols Transformation in Mycobacterium

作者：熊亮斌[1,2];孙吉[1];刘显舟[1];屈占国[1];计雨情[1];徐一新[1];王风清[2]

机构：[1]上海健康医学院协同科研中心/药学院,上海201318;[2]华东理工大学生物工程学院,上海200237

年份：2021

卷号：37

期号：10

起止页码：120

中文期刊名：生物技术通报

外文期刊名：Biotechnology Bulletin

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：国家自然科学基金项目(31370080);中国博士后面上基金(2020M671028);上海市卫生健康委员会临床研究专项(20204Y0380)。

语种：中文

中文关键词：新金色分枝杆菌;甾体药物中间体;中心代谢;9-OHAD;葡萄糖

外文关键词：Mycobacterium neoaurum;steroidal drug intermediate;central metabolism;9-OHAD;glucose

摘要：为探究新金色分枝杆菌代谢甾醇积累甾体药物中间体过程的中心代谢调节机制,采用转录组测序结合qRT-PCR技术,对比分析甾药中间体生产菌株中心代谢的关键基因转录水平,测定转化过程的葡萄糖消耗速率。结果显示,糖酵解途径的pfkB、pyk转录下调1.96倍及1.49倍;磷酸戊糖途径的zwf、gntZ转录下调3.57倍及2.43倍;三羧酸循环的citA、icd2和kdg转录分别下调2.5倍、1.78倍及1.92倍。对葡萄糖消耗速率的测定显示,中间体生产菌株的初始代谢速率显著低于野生型菌株。研究结果表明在转化甾醇积累甾药中间体过程中,分枝杆菌的中心代谢途径受到一定程度的抑制性调节。
To investigate the regulation mechanism of central metabolism during the transformation of sterols to steroidal drug intermediates in Mycobacterium neoaurum,RNA sequencing and qRT-PCR analysis were employed to analyze the transcriptional levels of key genes in the central metabolism of steroid drug intermediate-producing strains.Meanwhile,the glucose consuming rate during the transformation process was assessed.The results showed that the transcription of pfkB and pyk in glycolytic pathway was downregulated by 1.96-fold and 1.49-fold.The transcription of zwf and gntZ in pentose phosphate pathway was downregulated by 3.57-fold and 2.43-fold.And the citA,icd2 and kdg transcription were downregulated about 2.5-fold,1.78-fold and 1.92-fold,respectively.In addition,the determination of glucose consumption rate revealed that the initial metabolic rate of the steroidal intermediate-producing strain was significantly lower than that of the wild-type strain.This indicated that the central metabolic pathway of M.neoaurum was inhibited to some extent during the conversion of sterols to value-added steroidal intermediates.