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龟裂链霉菌M527新型次级代谢产物隐性基因簇的定向激活
结题报告
批准号:
31972320
项目类别:
面上项目
资助金额:
57.0 万元
负责人:
马正
依托单位:
学科分类:
生物防治
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
马正
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中文摘要
链霉菌是开发生物农药最重要的资源之一。随着植物病害的不断发生,开发新型生物农药迫在眉睫。前期链霉菌Streptomyces rimosus M527基因组测序发现,其至少有40个处于“沉默”或常规条件下不表达的合成次级代谢产物的“隐性基因簇”(Cryptic gene cluster),这为新天然产物的挖掘和生物农药的创制创造了条件。本项目根据S. rimosus M527基因组序列,采用基因组挖掘技术(Genome-mining)和生物信息学分析,对隐性基因簇的代谢产物进行预测,并筛选目标基因簇。采用途径调控因子改造、基因簇异源表达、报告基因标记与核糖体工程技术结合的突变株筛选等多种策略,实现新型聚酮/非核糖体肽隐性基因簇的定向激活。通过大规模发酵、化合物纯化和结构鉴定等,获得新型聚酮/非核糖体肽类化合物,并进行抑菌活性测试,以期产生具有生防潜力的新化合物,为生物农药的创制提供理想原料。
英文摘要
Streptomyces are one of the most important resources for developing biological pesticide. It is urgent to exploit novel biological pesticides with the increase of occurrence of plant-pathogenic diseases. It was observed that at least 40 biosynthetic secondary metabolites cryptic gene clusters which were silent and not expressed in laboratory condition were revealed in Streptomyces rimosus M527 by genome sequencing. It will provide the basis for exploitation of novel natural products and production of biological pesticide. In this study, based on the genome sequence of S. rimosus M527, genome-mining technology and bioinformatics analyses were employed to predict the putative metabolites and their structure of cryptic gene clusters and further to screen and identify the targeted gene cluster. Subsequently, the strategies such as modification of pathway-specific regulator, heterologous expression of gene cluster, and the isolation of mutants via reporter-guided combined with ribosome engineering technology, were used to activate the expressions of targeted gene clusters encoding novel PKS/NRPS. The fermentation products were purified and identified by using NMR experiments, and to produce the some novel PKS/NRPS. At the same time, the assays were conducted to evaluate antifungal activities, and further to discover novel products PKS/NRPS as potent antimicrobial agents and pesticides in agriculture field, which will supply the ideal material for production of biological pesticide.
期刊论文列表
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专利列表
DOI:10.1002/bit.28347
发表时间:2023-02-18
期刊:BIOTECHNOLOGY AND BIOENGINEERING
影响因子:3.8
作者:Shi,Yue;Zhang,Jinyao;Yu,Xiaoping
通讯作者:Yu,Xiaoping
DOI:10.1093/jimb/kuac030
发表时间:2023-02-13
期刊:Journal of industrial microbiology & biotechnology
影响因子:3.4
作者:
通讯作者:
DOI:10.1007/s00284-022-02867-9
发表时间:2022-06-01
期刊:CURRENT MICROBIOLOGY
影响因子:2.6
作者:Liao, Zhijun;Zhang, Jinyao;Yu, Xiaoping
通讯作者:Yu, Xiaoping
DOI:10.1016/j.tetlet.2023.154425
发表时间:2023-03
期刊:Tetrahedron Letters
影响因子:1.8
作者:Xiaoyu Pan;Yanhui Li;Shijie Yu;Huan Qi;Yu Liu;Xiachang Wang;Jidong Wang;Yongyong Zhang;Zheng Ma
通讯作者:Xiaoyu Pan;Yanhui Li;Shijie Yu;Huan Qi;Yu Liu;Xiachang Wang;Jidong Wang;Yongyong Zhang;Zheng Ma
DOI:--
发表时间:2020
期刊:中国生物防治学报
影响因子:--
作者:徐洁;胡叶锋;廖芷君;马正;俞晓平
通讯作者:俞晓平
Streptomyces rimosus M527特异性高强度合成龟裂霉素的多模块协同改造
  • 批准号:
    --
  • 项目类别:
    面上项目
  • 资助金额:
    54万元
  • 批准年份:
    2022
  • 负责人:
    马正
  • 依托单位:
全局性调控因子 NsdAsr 对龟裂霉素合成的调控机制研究
  • 批准号:
    LZ22C140002
  • 项目类别:
    省市级项目
  • 资助金额:
    0.0万元
  • 批准年份:
    2021
  • 负责人:
    马正
  • 依托单位:
龟裂霉素高效合成的分子机制解析及其理性设计改造
  • 批准号:
    31772213
  • 项目类别:
    面上项目
  • 资助金额:
    60.0万元
  • 批准年份:
    2017
  • 负责人:
    马正
  • 依托单位:
Streptomyces diastatochromogenes丰加霉素合成途径与调控机制解析
  • 批准号:
    31401792
  • 项目类别:
    青年科学基金项目
  • 资助金额:
    25.0万元
  • 批准年份:
    2014
  • 负责人:
    马正
  • 依托单位:
国内基金
海外基金