Dataset Information

Lysine Succinylation Contributes to Aflatoxin Production and Pathogenicity in Aspergillus flavus.

ABSTRACT: Aspergillus flavus (A. flavus) is a ubiquitous saprophytic and pathogenic fungus that produces the aflatoxin carcinogen, and A. flavus can have tremendous economic and health impacts worldwide. Increasing evidence demonstrates that lysine succinylation plays an important regulatory role in metabolic processes in both bacterial and human cells. However, little is known about the extent and function of lysine succinylation in A. flavus Here, we performed a global succinylome analysis of A. flavus using high accuracy nano-LC-MS/MS in combination with the enrichment of succinylated peptides from digested cell lysates and subsequent peptide identification. In total, 985 succinylation sites on 349 succinylated proteins were identified in this pathogen. Bioinformatics analysis revealed that the succinylated proteins were involved in various biological processes and were particularly enriched in the aflatoxin biosynthesis process. Site-specific mutagenesis and biochemical studies showed that lysine succinylation on the norsolorinic acid reductase NorA (AflE), a key enzyme in aflatoxins biosynthesis, can affect the production of sclerotia and aflatoxins biosynthesis in A. flavus. Together, our findings reveal widespread roles for lysine succinylation in regulating metabolism and aflatoxins biosynthesis in A. flavus Our data provide a rich resource for functional analyses of lysine succinylation and facilitate the dissection of metabolic networks in this pathogen.

SUBMITTER: Ren S

PROVIDER: S-EPMC5836371 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Lysine Succinylation Contributes to Aflatoxin Production and Pathogenicity in Aspergillus flavus.

Ren Silin S Yang Mingkun M Yue Yuewei Y Ge Feng F Li Yu Y Guo Xiaodong X Zhang Jia J Zhang Feng F Nie Xinyi X Wang Shihua S

Molecular & cellular proteomics : MCP 20180103 3

Aspergillus flavus (A. flavus) is a ubiquitous saprophytic and pathogenic fungus that produces the aflatoxin carcinogen, and A. flavus can have tremendous economic and health impacts worldwide. Increasing evidence demonstrates that lysine succinylation plays an important regulatory role in metabolic processes in both bacterial and human cells. However, little is known about the extent and function of lysine succinylation in A. flavus Here, we performed a global succin ...[more]

PMID: 29298838

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Project description:Aspergillus flavus is a common saprophytic and pathogenic fungus, and its secondary metabolic pathways are one of the most highly characterized owing to its aflatoxin (AF) metabolite affecting global economic crops and human health. Different natural environments can cause significant variations in AF synthesis. Succinylation was recently identified as one of the most critical regulatory post-translational modifications affecting metabolic pathways. It is primarily reported in human cells and bacteria with few studies on fungi. Proteomic quantification of lysine succinylation (Ksuc) exploring its potential involvement in secondary metabolism regulation (including AF production) has not been performed under natural conditions in A. flavus. In this study, a quantification method was performed based on tandem mass tag labeling and antibody-based affinity enrichment of succinylated peptides via high accuracy nano-liquid chromatography with tandem mass spectrometry to explore the succinylation mechanism affecting the pathogenicity of naturally isolated A. flavus strains with varying toxin production. Altogether, 1240 Ksuc sites in 768 proteins were identified with 1103 sites in 685 proteins quantified. Comparing succinylated protein levels between high and low AF-producing A. flavus strains, bioinformatics analysis indicated that most succinylated proteins located in the AF biosynthetic pathway were downregulated, which directly affected AF synthesis. Versicolorin B synthase is a key catalytic enzyme for heterochrome B synthesis during AF synthesis. Site-directed mutagenesis and biochemical studies revealed that versicolorin B synthase succinylation is an important regulatory mechanism affecting sclerotia development and AF biosynthesis in A. flavus. In summary, our quantitative study of the lysine succinylome in high/low AF-producing strains revealed the role of Ksuc in regulating AF biosynthesis. We revealed novel insights into the metabolism of AF biosynthesis using naturally isolated A. flavus strains and identified a rich source of metabolism-related enzymes regulated by succinylation.

Dataset Information

Lysine Succinylation Contributes to Aflatoxin Production and Pathogenicity in Aspergillus flavus.

Publications

Lysine Succinylation Contributes to Aflatoxin Production and Pathogenicity in <i>Aspergillus flavus</i>.

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