Fungal Metabolic Model for Tyrosinemia Type 3: Molecular Characterization of a Gene Encoding a 4-Hydroxy-Phenyl Pyruvate Dioxygenase from
            <i>Aspergillus nidulans</i>

Ferreira, Márcia Eliana da Silva; Savoldi, Marcela; Bonato, Pierina Sueli; Goldman, Maria Helena S.; Goldman, Gustavo Henrique

doi:10.1128/ec.00160-06

Cited by 6 publications

(7 citation statements)

References 19 publications

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“…However, HPPD is widely conserved in plants, animals, and microbes. In Aspergillus nidulans, 4-HPPD deletion mutant could not grow in the presence of phenylalanine and accumulated increased concentrations of tyrosine and 4-hydroxyphenylpyruvic acid [21]. Moreover, we found a higher sequence similarity of HPPD among fungi, which was consistent with higher inhabitation to other fungi (Figure 5).…”

Section: -Phenanthrol Inhibits Fungal Growth Through Disruption Of Ty...supporting

confidence: 71%

Transcriptome and Quasi-Targeted Metabolome Analyze Overexpression of 4-Hydroxyphenylpyruvate Dioxygenase Alleviates Fungal Toxicity of 9-Phenanthrol in Magnaporthe oryzae

Wang

Jibril

et al. 2022

IJMS

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Magnaporthe oryzae, the causal agent of rice blast disease, produces devastating damage to global rice production. It is urgent to explore novel strategies to overcome the losses caused by this disease. 9-phenanthrol is often used as a transient receptor potential melastatin 4 (TRPM4) channel inhibitor for animals, but we found its fungal toxicity to M. oryzae. Thus, we explored the antimicrobial mechanism through transcriptome and metabolome analyses. Moreover, we found that overexpression of a gene encoding 4-hydroxyphenylpyruvate dioxygenase involved in the tyrosine degradative pathway enhanced the tolerance of 9-phenanthrol in M. oryzae. Thus, our results highlight the potential fungal toxicity mechanism of 9-phenanthrol at metabolic and transcriptomic levels and identify a gene involving 9-phenanthrol alleviation. Importantly, our results demonstrate the novel mechanism of 9-phenanthrol on fungal toxicity that will provide new insights of 9-phenanthrol for application on other organisms.

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Section: -Phenanthrol Inhibits Fungal Growth Through Disruption Of Ty...supporting

confidence: 71%

Transcriptome and Quasi-Targeted Metabolome Analyze Overexpression of 4-Hydroxyphenylpyruvate Dioxygenase Alleviates Fungal Toxicity of 9-Phenanthrol in Magnaporthe oryzae

Wang

Jibril

et al. 2022

IJMS

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“…Phenylalanine is degraded by a series of enzymes to produce fumarate and acetoacetate. The catabolic pathway has been studied intensively in Aspergillus nidulans (Fernández‐Cañón and Peñalva, 1995, 1998; da Silva Ferreira et al ., 2006). The biosynthesis of aromatic amino acids is very active and they have been shown to be precursors of the dihydroxyphenylalanine (DOPA)–melanin pathway (Solomon et al ., 2004b).…”

Section: Resultsmentioning

confidence: 99%

Transcriptome analysis of Stagonospora nodorum: gene models, effectors, metabolism and pantothenate dispensability

Ipcho

Hane

Antoni

et al. 2011

Molecular Plant Pathology

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The wheat pathogen Stagonospora nodorum, causal organism of the wheat disease Stagonospora nodorum blotch, has emerged as a model for the Dothideomycetes, a large fungal taxon that includes many important plant pathogens. The initial annotation of the genome assembly included 16,586 nuclear gene models. These gene models were used to design a microarray that has been interrogated with labelled transcripts from six cDNA samples: four from infected wheat plants at time points spanning early infection to sporulation, and two time points taken from growth in artificial media. Positive signals of expression were obtained for 12,281 genes. This represents strong corroborative evidence of the validity of these gene models. Significantly differential expression between the various time points was observed. When infected samples were compared with axenic cultures, 2882 genes were expressed at a higher level in planta and 3630 were expressed more highly in vitro. Similar numbers were differentially expressed between different developmental stages. The earliest time points in planta were particularly enriched in differentially expressed genes. A disproportionate number of the early expressed gene products were predicted to be secreted, but otherwise had no obvious sequence homology to functionally characterized genes. These genes are candidate necrotrophic effectors. We have focused attention on genes for carbohydrate metabolism and the specific biosynthetic pathways active during growth in planta. The analysis points to a very dynamic adjustment of metabolism during infection. Functional analysis of a gene in the coenzyme A biosynthetic pathway showed that the enzyme was dispensable for growth, indicating that a precursor is supplied by the plant.

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“…Accumulation of intermediates of tyrosine catabolism results in cellular toxicity due to the production of intermediary metabolites or their spontaneous degradation products (4-hydroxyphenlpyruvic acid in hpdA mutants, homogentistic acid in hmgA mutants and succinylacetone and succinylacetoacetate from fumarylacetoacetate in fahA mutants) [ 7 , 8 , 10 , 32 , 33 ]. To investigate if toxic metabolites are accumulating in the P .…”

Section: Resultsmentioning

confidence: 99%

“…These results are in contrast to A . nidulans in which deletion of hpdA and maiA , but not hmgA , results in cellular toxicity [ 10 , 32 , 33 ]. These results suggest putative differences between the metabolites derived from homogentisate and 4-malelyacetate in P .…”

Section: Resultsmentioning

confidence: 99%

Intracellular Growth Is Dependent on Tyrosine Catabolism in the Dimorphic Fungal Pathogen Penicillium marneffei

et al. 2015

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During infection, pathogens must utilise the available nutrient sources in order to grow while simultaneously evading or tolerating the host’s defence systems. Amino acids are an important nutritional source for pathogenic fungi and can be assimilated from host proteins to provide both carbon and nitrogen. The hpdA gene of the dimorphic fungus Penicillium marneffei, which encodes an enzyme which catalyses the second step of tyrosine catabolism, was identified as up-regulated in pathogenic yeast cells. As well as enabling the fungus to acquire carbon and nitrogen, tyrosine is also a precursor in the formation of two types of protective melanin; DOPA melanin and pyomelanin. Chemical inhibition of HpdA in P. marneffei inhibits ex vivo yeast cell production suggesting that tyrosine is a key nutrient source during infectious growth. The genes required for tyrosine catabolism, including hpdA, are located in a gene cluster and the expression of these genes is induced in the presence of tyrosine. A gene (hmgR) encoding a Zn(II)2-Cys6 binuclear cluster transcription factor is present within the cluster and is required for tyrosine induced expression and repression in the presence of a preferred nitrogen source. AreA, the GATA-type transcription factor which regulates the global response to limiting nitrogen conditions negatively regulates expression of cluster genes in the absence of tyrosine and is required for nitrogen metabolite repression. Deletion of the tyrosine catabolic genes in the cluster affects growth on tyrosine as either a nitrogen or carbon source and affects pyomelanin, but not DOPA melanin, production. In contrast to other genes of the tyrosine catabolic cluster, deletion of hpdA results in no growth within macrophages. This suggests that the ability to catabolise tyrosine is not required for macrophage infection and that HpdA has an additional novel role to that of tyrosine catabolism and pyomelanin production during growth in host cells.

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Fungal Metabolic Model for Tyrosinemia Type 3: Molecular Characterization of a Gene Encoding a 4-Hydroxy-Phenyl Pyruvate Dioxygenase from Aspergillus nidulans

Cited by 6 publications

References 19 publications

Transcriptome and Quasi-Targeted Metabolome Analyze Overexpression of 4-Hydroxyphenylpyruvate Dioxygenase Alleviates Fungal Toxicity of 9-Phenanthrol in Magnaporthe oryzae

Transcriptome and Quasi-Targeted Metabolome Analyze Overexpression of 4-Hydroxyphenylpyruvate Dioxygenase Alleviates Fungal Toxicity of 9-Phenanthrol in Magnaporthe oryzae

Transcriptome analysis of Stagonospora nodorum: gene models, effectors, metabolism and pantothenate dispensability

Intracellular Growth Is Dependent on Tyrosine Catabolism in the Dimorphic Fungal Pathogen Penicillium marneffei

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