Biosynthesis and function of gliotoxin in Aspergillus fumigatus

被引：149

作者：

Scharf, Daniel H. ^{[1
,2
,3
]}

Heinekamp, Thorsten ^{[1
,2
]}

Remme, Nicole ^{[1
,2
,3
]}

Hortschansky, Peter ^{[1
,2
]}

Brakhage, Axel A. ^{[1
,2
,3
]}

Hertweck, Christian ^{[1
,2
,3
]}

机构：

[1] HKI, Leibniz Inst Nat Prod Res & Infect Biol, Dept Mol & Appl Microbiol, D-07745 Jena, Germany

[2] HKI, Leibniz Inst Nat Prod Res & Infect Biol, Dept Biomol Chem, D-07745 Jena, Germany

[3] Univ Jena, D-07745 Jena, Germany

来源：

APPLIED MICROBIOLOGY AND BIOTECHNOLOGY | 2012年 / 93卷 / 02期

关键词：

Aspergillus fumigatus; Non-ribosomal peptide biosynthesis; Gliotoxin; ETP toxins; NONRIBOSOMAL PEPTIDE SYNTHETASE; GENE-CLUSTER; BOND FORMATION; VIRULENCE; FUNGUS; GLIP; CONTRIBUTES; APOPTOSIS; DELETION;

D O I：

10.1007/s00253-011-3689-1

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Gliotoxin (GT) is the prototype of the epidithiodioxopiperazine (ETP)-type fungal toxins. GT plays a critical role in the pathobiology of Aspergillus fumigatus. It modulates the immune response and induces apoptosis in different cell types. The toxicity has been attributed to the unusual intramolecular disulfide bridge, which is the functional motif of all ETPs. Because of the extraordinary structure and activity of GT, this fungal metabolite has been the subject of many investigations. The biosynthesis of GT involves unprecedented reactions catalysed by recently discovered enzymes. Here, we summarize the recent progress in elucidating the GT biosynthetic pathway and its role in virulence.

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页码：467 / 472

页数：6

相关论文

共 39 条

[1] Functional analysis of a mitochondrial phosphopantetheinyl transferase (PPTase) gene pptB in Aspergillus fumigatus [J].

Allen, Gethin ;

Bromley, Mike ;

Kaye, Sarah J. ;

Keszenman-Pereyra, David ;

Zucchi, Tiago D. ;

Price, Jaqueline ;

Birch, Mike ;

Oliver, Jason D. ;

Turner, Geoffrey .

FUNGAL GENETICS AND BIOLOGY, 2011, 48 (04) :456-464

[2] GliP, a multimodular nonribosomal peptide synthetase in Aspergillus fumigatus, makes the diketopiperazine scaffold of gliotoxin [J].

Balibar, Carl J. ;

Walsh, Christopher T. .

BIOCHEMISTRY, 2006, 45 (50) :15029-15038

[3] THE STRUCTURE OF GLIOTOXIN [J].

BELL, MR ;

JOHNSON, JR ;

WILDI, BS ;

WOODWARD, RB .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1958, 80 (04) :1001-1001

[4] Aspergillus fumigatus inhibits angiogenesis through the production of gliotoxin and other secondary metabolites [J].

Ben-Ami, Ronen ;

Lewis, Russell E. ;

Leventakos, Konstantinos ;

Kontoyiannis, Dimitrios P. .

BLOOD, 2009, 114 (26) :5393-5399

[5] GliZ, a transcriptional regulator of gliotoxin biosynthesis, contributes to Aspergillus fumigatus virulence [J].

Bok, Jin Woo ;

Chung, DaWoon ;

Balajee, S. Arunmozhi ;

Marr, Kieren A. ;

Andes, David ;

Nielsen, Kristian Fog ;

Frisvad, Jens C. ;

Kirby, Katharine A. ;

Keller, Nancy P. .

INFECTION AND IMMUNITY, 2006, 74 (12) :6761-6768

[6] BIOSYNTHESIS OF GLIOTOXIN [J].

BULOCK, JD ;

LEIGH, C .

JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1975, (15) :628-629

[7] Disruption of a nonribosomal peptide synthetase in Aspergillus fumigatus eliminates gliotoxin production [J].

Cramer, Robert A., Jr. ;

Gamcsik, Michael P. ;

Brooking, Rhea M. ;

Najvar, Laura K. ;

Kirkpatrick, William R. ;

Patterson, Thomas F. ;

Balibar, Carl J. ;

Graybill, John R. ;

Perfect, John R. ;

Abraham, Soman N. ;

Steinbach, William J. .

EUKARYOTIC CELL, 2006, 5 (06) :972-980

[8] The Role of Glutathione S-Transferase GliG in Gliotoxin Biosynthesis in Aspergillus fumigatus [J].

Davis, Carol ;

Carberry, Stephen ;

Schrettl, Markus ;

Singh, Ishwar ;

Stephens, John C. ;

Barry, Sarah M. ;

Kavanagh, Kevin ;

Challis, Gregory L. ;

Brougham, Dermot ;

Doyle, Sean .

CHEMISTRY & BIOLOGY, 2011, 18 (04) :542-552

[9] Identification of Cryptic Products of the Gliotoxin Gene Cluster Using NMR-Based Comparative Metabolomics and a Model for Gliotoxin Biosynthesis [J].

Forseth, Ry R. ;

Fox, Ellen M. ;

Chung, DaWoon ;

Howlett, Barbara J. ;

Keller, Nancy P. ;

Schroeder, Frank C. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2011, 133 (25) :9678-9681

[10] The epipolythiodioxopiperazine (ETP) class of fungal toxins: distribution, mode of action, functions and biosynthesis [J].

Gardiner, DM ;

Waring, P ;

Howlett, BJ .

MICROBIOLOGY-SGM, 2005, 151 :1021-1032

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