The Putative Histone Methyltransferase DOT1 Regulates Aflatoxin and Pathogenicity Attributes in Aspergillus flavus

Li, Liang; Liu, Yinghang; Yang, Ke; Lin, Guinan; Xu, Zhangling; Lan, Huahui; Wang, Xiuna; Wang, Shihua

doi:10.3390/toxins9070232

Cited by 24 publications

(20 citation statements)

References 43 publications

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“…One contributing factor to this defect in pathogenicity is that conidiation dramatically decreased in the ΔaflO and K241R site mutants when compared with WT, and development is thought to be one of the main factors in pathogenicity of A. flavus (Amaike and Keller, 2011). On the other hand, acetylation at K241 might change the structure of AflO, leading to inactivation of methyltransferase activity, which is similar to the defect of pathogenicity in methyltransferase knockout mutants of A. flavus (Liang et al, 2017). All this evidence revealed that acetylation is critical for pathogenicity in A. flavus.…”

Section: Discussionmentioning

confidence: 99%

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Lysine acetylation contributes to development, aflatoxin biosynthesis and pathogenicity in Aspergillus flavus

Guang

Yue

Ren

et al. 2019

Environmental Microbiology

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Summary Aspergillus flavus is a pathogenic fungus that produces carcinogenic aflatoxins, posing a great threat to crops, animals and humans. Lysine acetylation is one of the most important reversible post‐translational modifications and plays a vital regulatory role in various cellular processes. However, current information on the extent and function of lysine acetylation and aflatoxin biosynthesis in A. flavus is limited. Here, a global acetylome analysis of A. flavus was performed by peptide pre‐fractionation, pan‐acetylation antibody enrichment and liquid chromatography–mass spectrometry. A total of 1313 high‐confidence acetylation sites in 727 acetylated proteins were identified in A. flavus. These acetylation proteins are widely involved in glycolysis/gluconeogenesis, pentose phosphate pathway, citric acid cycle and aflatoxin biosynthesis. AflO (O‐methyltransferase), a key enzyme in aflatoxin biosynthesis, was found to be acetylated at K241 and K384. Deletion of aflO not only impaired conidial and sclerotial developments, but also dramatically suppressed aflatoxin production and pathogenicity of A. flavus. Further site‐specific mutations showed that lysine acetylation of AflO could also result in defects in development, aflatoxin production and pathogenicity, suggesting that acetylation plays a vital role in the regulation of the enzymatic activity of AflO in A. flavus. Our findings provide evidence for the involvement of lysine acetylation in various biological processes in A. flavus and facilitating in the elucidation of metabolic networks.

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Section: Discussionmentioning

confidence: 99%

“…Previous studies have reported that methyltransferases participated in various stress responses in A. flavus (Liang et al, 2017;Zhi et al, 2017). Therefore, the potential role of AflO (O-methyltransferase) with response to cell wall integrity, genotoxic and oxidative stresses was examined.…”

Section: Aflo Response To Cell Wall Integrity Stress In a Flavusmentioning

confidence: 99%

Lysine acetylation contributes to development, aflatoxin biosynthesis and pathogenicity in Aspergillus flavus

Guang

Yue

Ren

et al. 2019

Environmental Microbiology

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“…Dot1 is a H3K79 methyltransferase in yeast, and has not been studied in filamentous fungi heavily. A dot1 homolog (AFLA_093140) in A. flavus has been deleted, and shown to transcriptionally regulate the aflatoxin BGC (Liang et al, 2017). However, it remains unclear if this homolog does in fact regulate H3K79 methylation, or how prevalent this modification is in filamentous fungi.…”

Section: Writing the Codementioning

confidence: 99%

On top of biosynthetic gene clusters: How epigenetic machinery influences secondary metabolism in fungi

Pfannenstiel

Keller

2019

Biotechnology Advances

132

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Fungi produce an abundance of bioactive secondary metabolites which can be utilized as antibiotics and pharmaceutical drugs. The genes encoding secondary metabolites are contiguously arranged in biosynthetic gene clusters (BGCs), which supports co-regulation of all genes required for any one metabolite. However, an ongoing challenge to harvest this fungal wealth is the finding that many of the BGCs are ‘silent’ in laboratory settings and lie in heterochromatic regions of the genome. Successful approaches allowing access to these regions - in essence converting the heterochromatin covering BGCs to euchromatin - include use of epigenetic stimulants and genetic manipulation of histone modifying proteins. This review provides a comprehensive look at the chromatin remodeling proteins which have been shown to regulate secondary metabolism, the use of chemical inhibitors used to induce BGCs, and provides future perspectives on expansion of epigenetic tools and concepts to mine the fungal metabolome.

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“…The cta1 deletion strain (ΔCTA1) and complementary strain (ΔCTA1:CTA1) were constructed according to previously described methods (Liang et al, 2017). Briefly, the upstream (AP) and downstream (BP) sequences of cta1 gene, as well as the pyrG gene of A. fumigatus were fused into the interruption fragment (AP-pyrG-BP) using fusion PCR strategy.…”

Section: Construction Of Mutantmentioning

confidence: 99%

Antioxidant‐related catalase CTA1 regulates development, aflatoxin biosynthesis, and virulence in pathogenic fungus Aspergillus flavus

Zhu

Yang

Bai

et al. 2020

Environmental Microbiology

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Summary Reactive oxygen species (ROS) induce the synthesis of a myriad of secondary metabolites, including aflatoxins. It raises significant concern as it is a potent environmental contaminant. In Aspergillus flavus., antioxidant enzymes link ROS stress response with coordinated gene regulation of aflatoxin biosynthesis. In this study, we characterized the function of a core component of the antioxidant enzyme catalase (CTA1) of A. flavus. Firstly, we verified the presence of cta1 corresponding protein (CTA1) by Western blot analysis and mass‐spectrometry based analysis. Then, the functional study revealed that the growth, sporulation and sclerotia formation significantly increased, while aflatoxins production and virulence were decreased in the cta1 deletion mutant as compared with the WT and complementary strains. Furthermore, the absence of the cta1 gene resulted in a significant rise in the intracellular ROS level, which in turn added to the oxidative stress level of cells. A further quantitative proteomics investigation hinted that in vivo, CTA1 might maintain the ROS level to facilitate the aflatoxin synthesis. All in all, the pleiotropic phenotype of A. flavus CTA1 deletion mutant revealed that the antioxidant system plays a crucial role in fungal development, aflatoxins biosynthesis and virulence.

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The Putative Histone Methyltransferase DOT1 Regulates Aflatoxin and Pathogenicity Attributes in Aspergillus flavus

Cited by 24 publications

References 43 publications

Lysine acetylation contributes to development, aflatoxin biosynthesis and pathogenicity in Aspergillus flavus

Lysine acetylation contributes to development, aflatoxin biosynthesis and pathogenicity in Aspergillus flavus

On top of biosynthetic gene clusters: How epigenetic machinery influences secondary metabolism in fungi

Antioxidant‐related catalase CTA1 regulates development, aflatoxin biosynthesis, and virulence in pathogenic fungus Aspergillus flavus

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