通过缺失植物致病真菌稻瘟病菌(Magnaporthe oryzae,又称稻梨孢菌Pyricularia oryzae)和亚洲镰孢菌中的HDA1型组蛋白去乙酰化酶来提高代谢产物产量。

Increased metabolite production by deletion of an HDA1-type histone deacetylase in the phytopathogenic fungi, Magnaporthe oryzae (Pyricularia oryzae) and Fusarium asiaticum.

作者信息

Maeda K, Izawa M, Nakajima Y, Jin Q, Hirose T, Nakamura T, Koshino H, Kanamaru K, Ohsato S, Kamakura T, Kobayashi T, Yoshida M, Kimura M

机构信息

Chemical Genetics Laboratory, RIKEN, Wako, Saitama, Japan.

Department of Biological Mechanisms and Function, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, Japan.

出版信息

Lett Appl Microbiol. 2017 Nov;65(5):446-452. doi: 10.1111/lam.12797. Epub 2017 Oct 10.

Abstract

UNLABELLED

Histone deacetylases (HDACs) play an important role in the regulation of chromatin structure and gene expression. We found that dark pigmentation of Magnaporthe oryzae (anamorph Pyricularia oryzae) ΔMohda1, a mutant strain in which an orthologue of the yeast HDA1 was disrupted by double cross-over homologous recombination, was significantly stimulated in liquid culture. Analysis of metabolites in a ΔMohda1 mutant culture revealed that the accumulation of shunt products of the 1,8-dihydroxynaphthalene melanin and ergosterol pathways were significantly enhanced compared to the wild-type strain. Northern blot analysis of the ΔMohda1 mutant revealed transcriptional activation of three melanin genes that are dispersed throughout the genome of M. oryzae. The effect of deletion of the yeast HDA1 orthologue was also observed in Fusarium asiaticum from the Fusarium graminearum species complex; the HDF2 deletion mutant produced increased levels of nivalenol-type trichothecenes. These results suggest that histone modification via HDA1-type HDAC regulates the production of natural products in filamentous fungi.

SIGNIFICANCE AND IMPACT OF THE STUDY

Natural products of fungi have significant impacts on human welfare, in both detrimental and beneficial ways. Although HDA1-type histone deacetylase is not essential for vegetative growth, deletion of the gene affects the expression of clustered secondary metabolite genes in some fungi. Here, we report that such phenomena are also observed in physically unlinked genes required for melanin biosynthesis in the rice blast fungus. In addition, production of Fusarium trichothecenes, previously reported to be unaffected by HDA1 deletion, was significantly upregulated in another Fusarium species. Thus, the HDA1-inactivation strategy may be regarded as a general approach for overproduction and/or discovery of fungal metabolites.

摘要

未标记

组蛋白去乙酰化酶(HDACs)在染色质结构和基因表达的调控中发挥重要作用。我们发现,稻瘟病菌(无性型为稻梨孢)ΔMohda1(一种通过双交换同源重组破坏酵母HDA1直系同源基因的突变菌株)在液体培养中黑色素沉着显著增加。对ΔMohda1突变体培养物中的代谢产物分析表明,与野生型菌株相比,1,8 - 二羟基萘黑色素和麦角固醇途径的分流产物积累显著增强。对ΔMohda1突变体的Northern印迹分析显示,在稻瘟病菌基因组中分散的三个黑色素基因发生转录激活。在禾谷镰刀菌物种复合体中的亚洲镰刀菌中也观察到酵母HDA1直系同源基因缺失的影响;HDF2缺失突变体产生的雪腐镰刀菌烯醇型单端孢霉烯水平增加。这些结果表明,通过HDA1型HDAC进行的组蛋白修饰调节丝状真菌中天然产物的产生。

研究的意义和影响

真菌的天然产物对人类福祉有重大影响,既有有害的一面,也有有益的一面。虽然HDA1型组蛋白去乙酰化酶对于营养生长不是必需的,但该基因的缺失会影响一些真菌中簇状次生代谢物基因的表达。在此,我们报道在稻瘟病菌黑色素生物合成所需的物理上不连锁的基因中也观察到这种现象。此外,先前报道不受HDA1缺失影响的镰刀菌单端孢霉烯的产生在另一种镰刀菌中显著上调。因此,HDA1失活策略可被视为一种用于过量生产和/或发现真菌代谢物的通用方法。

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