A nonribosomal peptide synthetase (Pes1) confers protection against oxidative stress in Aspergillus fumigatus

ABSTRACT The fungal secondary metabolite gliotoxin produced by Aspergillus fumigatus has been hypothesized to be important in the development of invasive aspergillosis. In this study, we addressed this hypothesis by disrupting a nonribosomal peptide synthetase (NRPS) (encoded by gliP) predicted to be involved in gliotoxin production. Mutants with a disrupted gliP locus failed to produce gliotoxin, which confirmed the role of the NRPS encoded by gliP in gliotoxin biosynthesis. We found no morphological, developmental, or physiological defects in ΔgliP mutant strains. In addition, disruption of gliP resulted in down regulation of gene expression in the gliotoxin biosynthesis gene cluster, which was restored with addition of exogenous gliotoxin. This interesting result suggests a role for gliotoxin in regulating its own production. Culture filtrates from the ΔgliP mutant were unable to inhibit ionomycin-dependent degranulation of mast cells, suggesting a role for gliotoxin in suppressing mast cell degranulation and possibly in disease development. However, the ΔgliP mutant did not have an impact on survival or tissue burden in a murine inhalational model of invasive aspergillosis. This result suggests that gliotoxin is not required for virulence in an immunosuppressed host with an invasive pulmonary infection.

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Faculty Opinions recommendation of Investigation of indigoidine synthetase reveals conserved active site base residue of nonribosomal peptide synthetase oxidases.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.738101115.793575536 ◽

2020 ◽

Author(s):

Zixin Deng ◽

Xudong Qu

Keyword(s):

Active Site ◽

Nonribosomal Peptide Synthetase ◽

Nonribosomal Peptide ◽

Peptide Synthetase

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Faculty Opinions recommendation of N-acylation during glidobactin biosynthesis by the tridomain nonribosomal peptide synthetase module GlbF.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.9511956.10161054 ◽

2011 ◽

Author(s):

Jan Grunewald

Keyword(s):

Nonribosomal Peptide Synthetase ◽

Nonribosomal Peptide ◽

Peptide Synthetase

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Draft Genome Sequence of Saccharomonospora sp. Strain LRS4.154, a Moderately Halophilic Actinobacterium with the Biotechnologically Relevant Polyketide Synthase and Nonribosomal Peptide Synthetase Systems

Genome Announcements ◽

10.1128/genomea.00392-17 ◽

2017 ◽

Vol 5 (21) ◽

Author(s):

Scarlett Alonso-Carmona ◽

Blanca Vera-Gargallo ◽

Rafael R. de la Haba ◽

Antonio Ventosa ◽

Horacio Sandoval-Trujillo ◽

...

Keyword(s):

Genome Sequence ◽

Polyketide Synthase ◽

Draft Genome ◽

Nonribosomal Peptide Synthetase ◽

Open Reading Frames ◽

Draft Genome Sequence ◽

Nonribosomal Peptide ◽

Moderately Halophilic ◽

Peptide Synthetase ◽

Reading Frames

ABSTRACT The draft genome sequence of Saccharomonospora sp. strain LRS4.154, a moderately halophilic actinobacterium, has been determined. The genome has 4,860,108 bp, a G+C content of 71.0%, and 4,525 open reading frames (ORFs). The clusters of PKS and NRPS genes, responsible for the biosynthesis of a large number of biomolecules, were identified in the genome.

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