Doyle, Sean and Jones, Gary W. and Dolan, Stephen K.
(2018)
Dysregulated gliotoxin biosynthesis attenuates the production of
unrelated biosynthetic gene cluster-encoded metabolites in Aspergillus fumigatus.
Fungal Biology, 122.
pp. 214-221.
ISSN 1878-6146
Abstract
Gliotoxin is an epipolythiodioxopiperazine (ETP) class toxin, contains a disulfide bridge that mediates its
toxic effects via redox cycling and is produced by the opportunistic fungal pathogen Aspergillus fumigatus.
The gliotoxin bis-thiomethyltransferase, GtmA, attenuates gliotoxin biosynthesis in A. fumigatus by
conversion of dithiol gliotoxin to bis-thiomethylgliotoxin (BmGT). Here we show that disruption of
dithiol gliotoxin bis-thiomethylation functionality in A. fumigatus results in significant remodelling of the
A. fumigatus secondary metabolome upon extended culture. RP-HPLC and LCeMS/MS analysis revealed
the reduced production of a plethora of unrelated biosynthetic gene cluster-encoded metabolites,
including pseurotin A, fumagillin, fumitremorgin C and tryprostatin B, occurs in A. fumigatus DgtmA upon
extended incubation. Parallel quantitative proteomic analysis of A. fumigatus wild-type and DgtmA during
extended culture revealed cognate abundance alteration of proteins encoded by relevant biosynthetic
gene clusters, allied to multiple alterations in hypoxia-related proteins. The data presented herein reveal
a previously concealed functionality of GtmA in facilitating the biosynthesis of other BGC-encoded
metabolites produced by A. fumigatus.
| Item Type: |
Article
|
| Keywords: |
BGC; Fungal proteomics; LC–MS; Metabolomics; Methyltransferase; NRPS; |
| Academic Unit: |
Faculty of Science and Engineering > Biology |
| Item ID: |
12397 |
| Identification Number: |
https://doi.org/10.1016/j.funbio.2017.12.007 |
| Depositing User: |
Dr. Sean Doyle
|
| Date Deposited: |
10 Feb 2020 17:19 |
| Journal or Publication Title: |
Fungal Biology |
| Publisher: |
Elsevier |
| Refereed: |
Yes |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
Repository Staff Only(login required)
 |
Item control page |
Downloads per month over past year
Origin of downloads
Altmetric
Altmetric