Journal
FUNGAL BIOLOGY
Volume 122, Issue 4, Pages 214-221Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.funbio.2017.12.007
Keywords
BGC; Fungal proteomics; LC-MS; Metabolomics; Methyltransferase; NRPS
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Funding
- Science Foundation Ireland Principal Investigator Award [PI/11/1188]
- Irish Research Council Embark PhD Fellowship
- Science Foundation Ireland [12/RI/2346 (3)]
- Irish Higher Education Authority
- Science Foundation Ireland (SFI) [12/RI/2346 (3)] Funding Source: Science Foundation Ireland (SFI)
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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 LC MS/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 Delta gtmA upon extended incubation. Parallel quantitative proteomic analysis of A. fumigatus wild-type and Delta gtmA 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. (C) 2017 British Mycological Society. Published by Elsevier Ltd. All rights reserved.
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