通过伏立诺他抑制组蛋白去乙酰化酶（HDAC）对aspergillus calidoustus 和 Aspergillus westerdijkiae 次生代谢产物谱的表观遗传调控。

Epigenetic modulation of secondary metabolite profiles in Aspergillus calidoustus and Aspergillus westerdijkiae through histone deacetylase (HDAC) inhibition by vorinostat.

机构信息

School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.

Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia.

出版信息

J Antibiot (Tokyo). 2020 Jun;73(6):410-413. doi: 10.1038/s41429-020-0286-5. Epub 2020 Feb 14.

DOI:10.1038/s41429-020-0286-5

PMID:32060485

Abstract

The effects of epigenetic modulation on secondary metabolite biosynthesis were investigated with five Aspergillus species cultured in the presence of either the DNA methyltransferase inhibitor 5-azacitidine or the histone deacetylase inhibitor vorinostat. With Aspergillus calidoustus and Aspergillus westerdijkiae, fermentation in the presence of vorinostat (100 μM) induced significant changes in secondary metabolite profile with examples of both induction and repression. We identified putative biosynthetic gene clusters for emericellamide in A. calidoustus and ochratoxin in A. westerdijkiae. A substantial induction in production levels was observed for two secondary metabolites: the diketopiperazine alkaloid phenylahistin in A. calidoustus and the polyketide penicillic acid in A. westerdijkiae, indicating the potential of epigenetic regulation for the activation of silent fungal biosynthetic pathways.

摘要

研究了 DNA 甲基转移酶抑制剂 5-氮杂胞苷或组蛋白去乙酰化酶抑制剂伏立诺他对五种曲霉属真菌次生代谢产物生物合成的表观遗传调节作用。在伏立诺他（100μM）存在的情况下，用 Aspergillus calidoustus 和 Aspergillus westerdijkiae 进行发酵，次生代谢产物图谱发生了显著变化，既有诱导也有抑制。我们鉴定了 A. calidoustus 中emericellamide 和 A. westerdijkiae 中ochratoxin 的可能生物合成基因簇。两种次生代谢产物的产量水平有显著提高：A. calidoustus 中的二酮哌嗪生物碱苯基ahistin 和 A. westerdijkiae 中的聚酮 penicillic acid，表明表观遗传调控有可能激活沉默的真菌生物合成途径。