In Vivo Evidence for a Prodrug Activation Mechanism during Colibactin Maturation

被引：104

作者：

Bian, Xiaoying ^{[1
,2
]}

Fu, Jun ^{[3
,4
]}

Plaza, Alberto ^{[1
,2
]}

Herrmann, Jennifer ^{[1
,2
]}

Pistorius, Dominik ^{[1
,2
]}

Stewart, A. Francis ^{[3
,4
]}

Zhang, Youming

Mueller, Rolf ^{[1
,2
]}

机构：

[1] Univ Saarland, Helmholtz Ctr Infect Res HZI, Helmholtz Inst Pharmaceut Res Saarland HIPS, Dept Microbial Nat Prod, D-66123 Saarbrucken, Germany

[2] Univ Saarland, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany

[3] Shandong Univ, State Key Lab Microbial Technol, Helmholtz Joint Inst Biotechnol, Jinan 250100, Peoples R China

[4] Tech Univ Dresden, Dept Genom, BioInnovat Zentrum, D-01307 Dresden, Germany

来源：

CHEMBIOCHEM | 2013年 / 14卷 / 10期

关键词：

biosynthesis; colibactin; E; coli Nissle; gene expression; prodrug maturation; BIOSYNTHETIC GENE-CLUSTER; CONSTITUENT AMINO-ACIDS; ESCHERICHIA-COLI; HOMOLOGOUS RECOMBINATION; ABSOLUTE-CONFIGURATION; RESISTANCE MECHANISM; ADENYLATION DOMAINS; MARFEYS METHOD; DIRECT CLONING; POLYKETIDE;

D O I：

10.1002/cbic.201300208

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Releasing the cytopath: We have identified an N-myristoyl-D-asparagine (1) as the free N-terminal prodrug scaffold in cytopathogenic Escherichia coli strains expressing the colibactin gene cluster. Colibactin is released in vivo upon cleavage of precolibactin. We provide for the first time in vivo evidence of the prodrug-like release mechanism of colibactin. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

引用

收藏

页码：1194 / 1197

页数：4

相关论文

共 24 条

[1]

Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota [J].

Arthur, Janelle C. ;

Perez-Chanona, Ernesto ;

Muehlbauer, Marcus ;

Tomkovich, Sarah ;

Uronis, Joshua M. ;

Fan, Ting-Jia ;

Campbell, Barry J. ;

Abujamel, Turki ;

Dogan, Belgin ;

Rogers, Arlin B. ;

Rhodes, Jonathan M. ;

Stintzi, Alain ;

Simpson, Kenneth W. ;

Hansen, Jonathan J. ;

Keku, Temitope O. ;

Fodor, Anthony A. ;

Jobin, Christian .

SCIENCE, 2012, 338 (6103) :120-123

[2]

Direct Cloning, Genetic Engineering, and Heterologous Expression of the Syringolin Biosynthetic Gene Cluster in E. coli through Red/ET Recombineering [J].

Bian, Xiaoying ;

Huang, Fan ;

Stewart, Francis A. ;

Xia, Liqiu ;

Zhang, Youming ;

Mueller, Rolf .

CHEMBIOCHEM, 2012, 13 (13) :1946-1952

[3]

A Prodrug Resistance Mechanism Is Involved in Colibactin Biosynthesis and Cytotoxicity [J].

Brotherton, Carolyn A. ;

Balskus, Emily P. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2013, 135 (09) :3359-3362

[4]

Predictive, structure-based model of amino acid recognition by nonribosomal peptide synthetase adenylation domains [J].

Challis, GL ;

Ravel, J ;

Townsend, CA .

CHEMISTRY & BIOLOGY, 2000, 7 (03) :211-224

[5]

Analysis of Structure-Function Relationships in the Colibactin-Maturating Enzyme ClbP [J].

Cougnoux, Antony ;

Gibold, Lucie ;

Robin, Frederic ;

Dubois, Damien ;

Pradel, Nathalie ;

Darfeuile-Michaud, Arlette ;

Dalmasso, Guillaume ;

Delmas, Julien ;

Bonnet, Richard .

JOURNAL OF MOLECULAR BIOLOGY, 2012, 424 (3-4) :203-214

[6]

Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells [J].

Cuevas-Ramos, Gabriel ;

Petit, Claude R. ;

Marcq, Ingrid ;

Boury, Michele ;

Oswald, Eric ;

Nougayrede, Jean-Philippe .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (25) :11537-11542

[7]

ClbP Is a Prototype of a Peptidase Subgroup Involved in Biosynthesis of Nonribosomal Peptides [J].

Dubois, Damien ;

Baron, Olivier ;

Cougnoux, Antony ;

Delmas, Julien ;

Pradel, Nathalie ;

Boury, Michele ;

Bouchon, Bernadette ;

Bringer, Marie-Agnes ;

Nougayrede, Jean-Philippe ;

Oswald, Eric ;

Bonnet, Richard .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (41) :35562-35570

[8]

Assembly-line enzymology for polyketide and nonribosomal peptide antibiotics: Logic, machinery, and mechanisms [J].

Fischbach, Michael A. ;

Walsh, Christopher T. .

CHEMICAL REVIEWS, 2006, 106 (08) :3468-3496

[9]

Full-length RecE enhances linear-linear homologous recombination and facilitates direct cloning for bioprospecting [J].

Fu, Jun ;

Bian, Xiaoying ;

Hu, Shengbaio ;

Wang, Hailong ;

Huang, Fan ;

Seibert, Philipp M. ;

Plaza, Alberto ;

Xia, Liqiu ;

Mueller, Rolf ;

Stewart, A. Francis ;

Zhang, Youming .

NATURE BIOTECHNOLOGY, 2012, 30 (05) :440-+

[10]

Efficient transfer of two large secondary metabolite pathway gene clusters into heterologous hosts by transposition [J].

Fu, Jun ;

Wenzel, Silke C. ;

Perlova, Olena ;

Wang, Junping ;

Gross, Frank ;

Tang, Zhiru ;

Yin, Yulong ;

Stewart, A. Francis ;

Mueller, Rolf ;

Zhang, Youming .

NUCLEIC ACIDS RESEARCH, 2008, 36 (17) :e113