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Manzanares-Miralles L, Sarikaya-Bayram O, Smith EB, Dolan SK, Bayram O, Jones GW, Doyle S (2016) Quantitative proteomics reveals the mechanism and consequence of gliotoxin-mediated dysregulation of the methionine cycle in Aspergillus niger. J Proteomics 131:149-62
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Abstract:Gliotoxin (GT) is a redox-active metabolite, produced by Aspergillus fumigatus, which inhibits the growth of other fungi. Here we demonstrate how A. Niger responds to GT exposure. Quantitative proteomics revealed that GT dysregulated the abundance of 378 proteins including those involved in methionine metabolism and induced de novo abundance of two S-adenosylmethionine (SAM)-dependent methyltransferases. Increased abundance of enzymes S-adenosylhomocysteinase (p=0.0018) required for homocysteine generation from S-adenosylhomocysteine (SAH), and spermidine synthase (p=0.0068), involved in the recycling of Met, was observed. Analysis of Met-related metabolites revealed significant increases in the levels of Met and adenosine, in correlation with proteomic data. Methyltransferase MT-II is responsible for bisthiobis(methylthio)gliotoxin (BmGT) formation, deletion of MT-II abolished BmGT formation and led to increased GT sensitivity in A. Niger. Proteomic analysis also revealed that GT exposure also significantly (p<0.05) increased hydrolytic enzyme abundance, including glycoside hydrolases (n=22) and peptidases (n=16). We reveal that in an attempt to protect against the detrimental affects of GT, methyltransferase-mediated GT thiomethylation alters cellular pathways involving Met and SAM, with consequential dysregulation of hydrolytic enzyme abundance in A. Niger. Thus, it provides new opportunities to exploit the response of GT-naive fungi to GT.
Status:PublishedType:Journal ArticlePubMed ID:26498071


Topics addressed in this paper
There are 78 different genes addressed in this paper.

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Topics
Genes linked to topics(#1-10)
An01g01720
(A. niger)
An01g01750
(A. niger)
An01g14920
(A. niger)
An02g01830
(A. niger)
An02g04690
(A. niger)
An02g06300
(A. niger)
An02g07430
(A. niger)
An02g10750
(A. niger)
An02g11940
(A. niger)
An02g13920
(A. niger)
Aspergillus niger
Large-scale protein detection

Topics
Genes linked to topics(#11-20)
An03g00500
(A. niger)
An03g01010
(A. niger)
An04g01800
(A. niger)
An04g01870
(A. niger)
An04g06380
(A. niger)
An05g00050
(A. niger)
An05g01870
(A. niger)
An05g02410
(A. niger)
An06g00190
(A. niger)
An06g00310
(A. niger)
Aspergillus niger
Large-scale protein detection

Topics
Genes linked to topics(#21-30)
An07g07700
(A. niger)
An08g01960
(A. niger)
An08g05790
(A. niger)
An08g06560
(A. niger)
An08g07350
(A. niger)
An08g08910
(A. niger)
An09g02830
(A. niger)
An09g05480
(A. niger)
An11g09510
(A. niger)
An11g11180
(A. niger)
Aspergillus niger
Large-scale protein detection
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Topics
Genes linked to topics(#31-40)
An12g05960
(A. niger)
An14g04240
(A. niger)
An15g01420
(A. niger)
An15g01890
(A. niger)
An16g05570
(A. niger)
An16g06750
(A. niger)
An16g08150
(A. niger)
An18g01320
(A. niger)
MT-II
(A. niger)
aamA
(A. niger)
Aspergillus niger
Large-scale protein detection

Topics
Genes linked to topics(#41-50)
agdA
(A. niger)
agdB
(A. niger)
aglA
(A. niger)
aglB
(A. niger)
agsA
(A. niger)
agsE
(A. niger)
agtA
(A. niger)
agtC
(A. niger)
amyC
(A. niger)
ape3
(A. niger)
Aspergillus niger
Large-scale protein detection

Topics
Genes linked to topics(#51-60)
apsA
(A. niger)
bgtB
(A. niger)
crhD
(A. niger)
ctcA
(A. niger)
dfgC
(A. niger)
eglB
(A. niger)
exsG
(A. niger)
gbeA
(A. niger)
gdbA
(A. niger)
gelA
(A. niger)
Aspergillus niger
Large-scale protein detection
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Topics
Genes linked to topics(#61-70)
gelD
(A. niger)
glaA
(A. niger)
lacA
(A. niger)
mdh1
(A. niger)
mdhA
(A. niger)
mndA
(A. niger)
msdS
(A. niger)
nag1
(A. niger)
papA
(A. niger)
pepA
(A. niger)
Aspergillus niger
Large-scale protein detection

Topics
Genes linked to topics(#71-78)
pepAb
(A. niger)
pepC
(A. niger)
pepF
(A. niger)
protA
(A. niger)
protB
(A. niger)
protC
(A. niger)
protF
(A. niger)
sC
(A. niger)
Aspergillus niger
Large-scale protein detection
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