Histone Deacetylase UvHST2 Is a Global Regulator of Secondary Metabolism in Ustilaginoidea virens

Abstract

Ustilaginoidea virens, the causal agent of rice false smut, produces a large amount of mycotoxins, including ustilaginoidins and sorbicillinoids. However, little is known about the regulatory mechanism of mycotoxin biosynthesis inU. virens.Here, we demonstrate that the NAD + -dependent histone deacetylase UvHST2 negatively regulates ustilaginoidin biosynthesis. UvHst2 knockout caused retarded hypha growth and reduced conidiation and pathogenicity inU. virens. Transcriptome analysis revealed that the transcription factor genes, transporter genes, and other tailoring genes in eight biosynthetic gene clusters (BGCs) including ustilaginoidin and sorbicillinoid BGCs were upregulated in ΔUvhst2. Interestingly, the UvHst2 deletion affects alternative splicing. Metabolomics revealed that UvHST2 negatively regulates the biosynthesis of various mycotoxins including ustilaginoidins, sorbicillin, ochratoxin B, zearalenone, and O-M-sterigmatocystin. Combined transcriptome and metabolome analyses uncover that UvHST2 positively regulates pathogenicity but negatively modulates the expression of BGCs involved in secondary metabolism. Collectively, UvHST2 functions as a global regulator of secondary metabolism inU. virens.

UvHOS3‐mediated histone deacetylation is essential for virulence and negatively regulates ustilaginoidin biosynthesis in Ustilaginoidea virens

“…The culture of U. virens generates multiple types of mycotoxins, such as ustilaginoidins and sorbicillinoids (Liu, Wang, et al., 2023 ; Zhang, Xu, et al., 2022 ). The mycotoxin biosynthesis‐related genes in DEGs are summarized in Table S7 .…”

“…Ustilaginoidins, one of the major types of mycotoxins in U. virens , are toxic to humans and livestock and threaten food safety. Although HDACs have been reported to be key players in regulating gene expression and secondary metabolism in fungi, knowledge about HDAC functions in virulence and mycotoxin biosynthesis in U. virens is scarce (Liu, Wang, et al., 2023 ). In this study, we not only demonstrated that a class II HDAC UvHOS3 positively regulates vegetative growth and development, conidiation and pathogenicity, but also revealed that UvHOS3 inhibits biosynthesis of mycotoxins, especially ustilaginoidins and sorbicillinoids in U. virens .…”

“…Metabolomic analysis revealed that multiple types of mycotoxins, including ochratoxin B, zearalenones, zeranol, mycotoxin T2, aflatoxin B1, aflatoxin G2 (Fang et al., 2022 ; Janik‐Karpinska et al., 2023 ; Luo et al., 2022 ; Peng et al., 2023 ) and ustilaginoidin D (Wang et al., 2021 ) that pose a health risk to people and animals were accumulated significantly in the Δ Uvhos3 mutant (Figure 4c ). Interestingly, the mycotoxins ochratoxin B, zearalenone and O‐M‐sterigmatocystin are also accumulated to a higher level when the class III HDAC gene UvHst2 is deleted in U. virens (Liu, Wang, et al., 2023 ). The correlation analyses of the differential metabolites and DEGs in the Δ Uvhos3 (Figure 8 ) and Δ Uvhst2 mutants (Liu, Wang, et al., 2023 ) showed that UV8b_03320 was involved in regulating the accumulation of multiple metabolites.…”

“…Interestingly, the mycotoxins ochratoxin B, zearalenone and O‐M‐sterigmatocystin are also accumulated to a higher level when the class III HDAC gene UvHst2 is deleted in U. virens (Liu, Wang, et al., 2023 ). The correlation analyses of the differential metabolites and DEGs in the Δ Uvhos3 (Figure 8 ) and Δ Uvhst2 mutants (Liu, Wang, et al., 2023 ) showed that UV8b_03320 was involved in regulating the accumulation of multiple metabolites. These results demonstrate that HDACs are important regulators of mycotoxin biosynthesis in U. virens .…”

“…In filamentous fungi, epigenetic modification, such as histone acetylation and deacetylation, plays an important role in the regulation of fungal growth and development, tolerance to external stresses, secondary metabolism and pathogenicity (Fan et al., 2017 ; Liu, Wang, et al., 2023 ; Macheleidt et al., 2016 ; Wiemann et al., 2013 ; Yin et al., 2019 ; Zhang, Guo, et al., 2022 ). Histone is acetylated by histone acetyltransferases (HATs), which is reversed by histone deacetylases (HDACs; Ma et al., 2013 ).…”