Duplication and Functional Divergence of Branched-Chain Amino Acid Biosynthesis Genes in Aspergillus nidulans

Steyer, Joel T; Downes, Damien J.; Hunter, Cameron C.; Migeon, Pierre; Todd, Richard B.

doi:10.1128/mbio.00768-21

Cited by 10 publications

(12 citation statements)

References 96 publications

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“…More specifically, wave 1 was enriched for GO terms associated with RNA-binding and the synthesis of branched amino acids. Branched amino acids play an important role in fungal pathogenesis [67–69], with leucine metabolism shown to be crucial for host infection by M. oryzae and Fusarium graminearum [68], and methionine biosynthesis found to be associated with the regulation of multiple cellular processes [69, 70]. The early expression of genes associated with the synthesis of branched amino acids and methionine could suggest a similar crucial role for these amino acids in the pathogenesis of V. inaequalis .…”

Section: Discussionmentioning

confidence: 99%

TheVenturia inaequaliseffector repertoire is expressed in waves and is dominated by expanded families with predicted structural similarity to avirulence proteins from other plant-pathogenic fungi

Rocafort

Bowen

Hassing

et al. 2022

Preprint

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BackgroundScab, caused by the biotrophic fungus Venturia inaequalis, is the most economically important disease of apples worldwide. During infection, V. inaequalis occupies the subcuticular environment, where it secretes virulence factors, termed effectors, to promote host colonization. However, in the presence of corresponding host resistance proteins, these effectors are recognized as avirulence determinants to activate plant defences. To develop durable control strategies against scab, a better understanding of the molecular mechanisms underpinning subcuticular growth by V. inaequalis is required. Likewise, more information is needed on the role that effectors play in activating, suppressing or circumventing resistance protein-mediated defences.ResultsWe generated the first comprehensive RNA-seq transcriptome of V. inaequalis during colonization of apple. Analysis of this transcriptome revealed five in planta gene expression clusters or waves corresponding to three specific infection stages: early, mid and mid-late infection. Early infection was characterized by genes encoding plant cell wall-degrading enzymes (PCWDEs) and proteins associated with oxidative stress responses. Mid infection was characterized by genes encoding transporter proteins. Finally, mid-late infection was characterized by genes encoding PCWDEs and effector candidates (ECs), with most ECs belonging to expanded protein families. To gain insights into function, AlphaFold2 was used to predict the tertiary structures of proteinaceous ECs. Strikingly, many ECs were predicted to have structural similarity to avirulence proteins from other plant-pathogenic fungi, including members of the MAX, LARS, ToxA and FOLD structural effector families. In addition, several other ECs, including an EC family with amino acid similarity to the AvrLm6 effector from Leptosphaeria maculans, were predicted to adopt a KP6/ferredoxin-like fold. Thus, proteins with a KP6/ferredoxin-like fold may represent yet another structural family of effectors shared among plant-pathogenic fungi.ConclusionsOur study reveals the transcriptomic profile underpinning subcuticular growth by V. inaequalis, and reinforces the idea that fungal effectors share a limited number of structural folds. Importantly, our study also provides an enriched list of V. inaequalis ECs that can be investigated for roles in virulence and avirulence, and raises the possibility that apple resistance proteins can be engineered to recognize EC family folds or host components targeted by multiple EC family members.

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Section: Discussionmentioning

confidence: 99%

TheVenturia inaequaliseffector repertoire is expressed in waves and is dominated by expanded families with predicted structural similarity to avirulence proteins from other plant-pathogenic fungi

Rocafort

Bowen

Hassing

et al. 2022

Preprint

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“…Interestingly, the two potential BAT genes (batA and batC) are not significantly regulated by any of the supplementations, suggesting a requirement for both BCAA biosynthesis and degradation. This sharply contrasts the BCAA-dependent transcriptional regulation of BAT genes in other fungi [2,6,26].…”

Section: Transcriptional Regulation Of Bcaa Biosynthesismentioning

confidence: 60%

“…The final step in BCAA biosynthesis is the conversion of α-keto acids to Ile, Leu, and Val and is catalysed by branched-chain amino acid aminotransferases (BATs), whose genes are present in multiple copies in ascomycetes [26]. However, the M. alpina genome encodes solely one mitochondrial BAT-homologue (BatA).…”

Section: Identification Of Bcaa Biosynthetic Genes In M Alpinamentioning

confidence: 99%

“…The BCAA aminotransferases (BAT) catalyse the final step in BCAA biosynthesis and the first step in BCAA degradation, i.e., the transamination of an α-keto acid to its respective BCAA and vice versa. Interestingly, genomes of ascomycetes usually encode at least two-usually inversely regulated-genes for BATs for anabolic BCAA biosynthesis and BCAA catabolism, respectively [26]. However, the genome of M. alpina encodes only one enzyme (BatA, 45.2 kDa).…”

Section: Biochemical Characterization Of Batamentioning

confidence: 99%

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Regulation of the Leucine Metabolism in Mortierella alpina

Sonnabend

Seiler

Gressler

2022

JoF

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The oleaginous fungus Mortierella alpina is a safe source of polyunsaturated fatty acids (PUFA) in industrial food and feed production. Besides PUFA production, pharmaceutically relevant surface-active and antimicrobial oligopeptides were isolated from this basal fungus. Both production of fatty acids and oligopeptides rely on the biosynthesis and high turnover of branched-chain-amino acids (BCAA), especially l-leucine. However, the regulation of BCAA biosynthesis in basal fungi is largely unknown. Here, we report on the regulation of the leucine, isoleucine, and valine metabolism in M. alpina. In contrast to higher fungi, the biosynthetic genes for BCAA are hardly transcriptionally regulated, as shown by qRT-PCR analysis, which suggests a constant production of BCAAs. However, the enzymes of the leucine metabolism are tightly metabolically regulated. Three enzymes of the leucine metabolism were heterologously produced in Escherichia coli, one of which is inhibited by allosteric feedback loops: The key regulator is the α-isopropylmalate synthase LeuA1, which is strongly disabled by l-leucine, α-ketoisocaproate, and propionyl-CoA, the precursor of the odd-chain fatty acid catabolism. Its gene is not related to homologs from higher fungi, but it has been inherited from a phototrophic ancestor by horizontal gene transfer.

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“…Valine, leucine, and isoleucine form the small group of branched chain amino acids (BCAAs), which are synthesized in bacteria, plants, and fungi, but not in animals [1,2]. The biosynthesis of these amino acids shows high similarity between organisms of the different kingdoms of life, of which valine and isoleucine synthesis are carried out by the same enzymes, and leucine is created from α-ketoisovalerate (a transamination precursor of valine) [3].…”

Section: Introductionmentioning

confidence: 99%

Functional Analysis of Keto-Acid Reductoisomerase ILVC in the Entomopathogenic Fungus Metarhizium robertsii

Wang

Liu

Yin

et al. 2021

JoF

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Ketol-acid reductoisomerase (ILVC) is the second enzyme in the branched-chain amino acid (BCAA) biosynthesis, which regulates many physiological activities in a variety of organisms from bacteria to fungi and plants. In this work, function mechanisms of ILVC in Metarhizium robertsii Metchnikoff (Hypocreales: Clavicipitaceae) were explored with site-directed mutagenesis, reductase activity assays and transcriptomics analysis. The reductase activity assays showed that ILVC from phytopathogenic fungi exhibited significantly higher activities than those from entomopathogenic fungi but lower than those from yeast. Site-directed mutagenesis and enzymatic activities of MrILVC with different active-site mutants (Arg-113, Ser-118, Asp-152, Asp-260, and Glu-264) confirmed that active sites of MrILVC are conserved with plant and bacterial ILVCs. Deleting MrilvC causes the complete failures of vegetative growth and conidial germination, feeding with branched-chain amino acids (BCAAs) recovers the fungal growth but not conidial germination, while both characteristics are restored when supplemented with yeast extract. Compared to ΔMrilvC cultured in czapek agar (CZA), plenty of genes involved in the biosynthesis of antibiotics and amino acids were up- or down-regulated in the wild type or ΔMrilvC feeding with either BCAAs or yeast extract. Further analysis showed some genes, such as catalase A, participate in mycelial growth and conidial germination was down-regulated in ΔMrilvC from CZA, revealing that MrILVC might control the fungal development by gene regulation and BCAAs or yeast extract could play partial roles of MrILVC. This study will advance our understanding of ILVC function mechanisms in fungi.

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Duplication and Functional Divergence of Branched-Chain Amino Acid Biosynthesis Genes in Aspergillus nidulans

Abstract: Branched-chain amino acid (BCAA) biosynthesis is important for pathogenic fungi to successfully cause disease in human and plant hosts. The enzymes for their production are absent from humans and, therefore, provide potential antifungal targets.

Cited by 10 publications

References 96 publications

TheVenturia inaequaliseffector repertoire is expressed in waves and is dominated by expanded families with predicted structural similarity to avirulence proteins from other plant-pathogenic fungi

TheVenturia inaequaliseffector repertoire is expressed in waves and is dominated by expanded families with predicted structural similarity to avirulence proteins from other plant-pathogenic fungi

Regulation of the Leucine Metabolism in Mortierella alpina

Functional Analysis of Keto-Acid Reductoisomerase ILVC in the Entomopathogenic Fungus Metarhizium robertsii

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