青霉菌组蛋白去乙酰化酶基因的敲除及其次级代谢产物变化

doi:10.3976/j.issn.1002-4026.2021.01.003

山东科学 ›› 2021, Vol. 34 ›› Issue (1): 21-27.doi: 10.3976/j.issn.1002-4026.2021.01.003

青霉菌组蛋白去乙酰化酶基因的敲除及其次级代谢产物变化

赵佩佩¹，刘海溶¹，杨梦¹，王红²，齐君¹，刘昌衡¹，夏雪奎^1*

1.齐鲁工业大学（山东省科学院），山东省科学院生物研究所，山东济南 250103；2.山东师范大学生命科学院学院，山东济南 250014

收稿日期:2020-06-01 出版日期:2021-02-15 发布日期:2021-01-29
通信作者: 夏雪奎。Tel：0531-82605332，E-mail：xiaxk@sdas.org E-mail:xiaxk@sdas.org
作者简介:赵佩佩（1989—），女，助理研究员，研究方向为分子生物学。
基金资助:
国家自然科学基金面上项目（31770024）；山东省自然科学基金面上项目（ZR2017MH025）；山东省“泰山学者”计划

Histone deacetylase gene knockout in Penicillium and changes in secondary metabolite production

ZHAO Pei-pei¹,LIU Hai-rong¹,YANG Meng¹,WANG Hong²,QI Jun¹,LIU Chang-heng¹，XIA Xue-kui^1*

1.Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China;2. College of Life Science, Shandong Normal University, Jinan 250014, China

Received:2020-06-01 Online:2021-02-15 Published:2021-01-29

摘要/Abstract

摘要： 丝状真菌尤其是青霉菌Penicillium代谢的各类次级产物日趋成为研制新药的重要来源，很多药物如抗癌药物、抗生素、免疫抑制剂等均来源于真菌。然而真菌次级代谢受多因素的影响，其中表观遗传修饰起到重要的调控作用。组蛋白乙酰化表观遗传修饰常与转录激活相关，从而促进次级代谢产物的合成。以青霉属真菌Penicillium christenseniae SD-193.84为研究对象，利用生物信息学手段确定其组蛋白去乙酰化酶（HDAC）基因，建立该菌中同源重组基因敲除技术，对该基因进行敲除，并比较了基因敲除前后次级代谢产物的变化，发现HDAC影响了多种次级代谢产物的合成。本研究为青霉菌分子遗传操作及次级代谢调控提供了参考。

关键词: 组蛋白去乙酰化酶, 青霉菌, 表观遗传修饰, 次级代谢产物, 基因敲除

Abstract: Various secondary metabolites produced by filamentous fungi, especially Penicillium, are becoming an important source of new drugs. Many drugs such as anticancer drugs, antibiotics, and immunosuppressants are derived from fungal secondary metabolites. However, the secondary metabolism of fungi is affected by many factors, among which epigenetic modification plays an important regulatory role. The epigenetic modification by histone acetylation is often associated with transcriptional activation, thereby facilitating the synthesis of secondary metabolites. In this study, Penicillium christenseniae SD-193.84 was used as the research object. Bioinformatics methods were used to identify the histone deacetylase(HDAC) gene. A gene knockout technique based on homologous recombination was established in this fungus to knock out HDAC. Analysis of secondary metabolites was conducted before and after the gene knockout. We found that HDAC affects the synthesis of a variety of secondary metabolites in the fungus. This study provides a reference for molecular genetic manipulation and secondary metabolic regulation in Penicillium.

Key words: histone deacetylase, Penicillium, epigenetic modification, secondary metabolites;gene knockout

中图分类号:

Q935

赵佩佩, 刘海溶, 杨梦, 王红, 齐君, 刘昌衡, 夏雪奎. 青霉菌组蛋白去乙酰化酶基因的敲除及其次级代谢产物变化 [J]. 山东科学, 2021, 34(1): 21-27.

ZHAO Pei-pei, LIU Hai-rong, YANG Meng, WANG Hong, QI Jun, LIU Chang-heng, XIA Xue-kui. Histone deacetylase gene knockout in Penicillium and changes in secondary metabolite production[J]. Shandong Science, 2021, 34(1): 21-27.

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青霉菌组蛋白去乙酰化酶基因的敲除及其次级代谢产物变化

Histone deacetylase gene knockout in Penicillium and changes in secondary metabolite production

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