Mycolactones: immunosuppressive and cytotoxic polyketides produced by aquatic mycobacteria

被引：84

作者：

Hong, Hui ^{[3
]}

Demangel, Caroline ^{[2
]}

Pidot, Sacha J. ^{[1
]}

Leadlay, Peter F. ^{[3
]}

Stinear, Tim ^{[1
]}

机构：

[1] Monash Univ, Dept Microbiol, Clayton, Vic 3800, Australia

[2] Inst Pasteur, Unite Postulante Pathogenom, F-75015 Paris, France

[3] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England

来源：

NATURAL PRODUCT REPORTS | 2008年 / 25卷 / 03期

基金：

英国惠康基金;

关键词：

D O I：

10.1039/b803101k

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mycolactones are a family of highly related macrocyclic polyketides that exhibit immunosuppressive and cytotoxic properties. First discovered in 1999, they are the primary virulence factors produced by the environmental human pathogen Mycobacterium ulcerans, the causative agent of Buruli ulcer, and by some closely-related aquatic mycobacteria that cause disease in fish and frogs. Mycolactones are characterized by a common 12-membered lactone core to which is appended an unsaturated fatty acyl side-chain of variable length and oxidation state. This Highlight summarizes recent progress in understanding the structural diversity of the mycolactones, their biological activity and mode of action in mammalian cells, and the genetics, evolution, and enzymology of their biosynthesis.

引用

页码：447 / 454

页数：8

共 54 条

[1] Mycobacterium ulcerans toxic macrolide, mycolactone modulates the host immune response and cellular location of M-ulcerans in vitro and in vivo [J].

Adusumilli, S ;

Mve-Obiang, A ;

Sparer, T ;

Meyers, W ;

Hayman, J ;

Small, PLC .

CELLULAR MICROBIOLOGY, 2005, 7 (09) :1295-1304

[2] Synthesis of the mycolactone core by ring-closing metathesis [J].

Alexander, Matthew D. ;

Fontaine, Shaun D. ;

La Clair, James J. ;

DiPasquale, Antonio G. ;

Rheingold, Arnold L. ;

Burkart, Michael D. .

CHEMICAL COMMUNICATIONS, 2006, (44) :4602-4604

[3] Organization of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: Analysis of the enzymatic domains in the modular polyketide synthase [J].

Aparicio, JF ;

Molnar, I ;

Schwecke, T ;

Konig, A ;

Haydock, SF ;

Khaw, LE ;

Staunton, J ;

Leadlay, PF .

GENE, 1996, 169 (01) :9-16

[4]

BALI S, 2007, CHEMBIOCHEM, V8, P2043

[5] Stereochemistry of the core structure of the mycolactones [J].

Benowitz, AB ;

Fidanze, S ;

Small, PLC ;

Kishi, Y .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2001, 123 (21) :5128-5129

[6] Suspension cultivation of Mycobacterium ulcerans for the production of mycolactones [J].

Cadapan, LD ;

Arslanian, RL ;

Carney, JR ;

Zavala, SM ;

Small, PL ;

Licari, P .

FEMS MICROBIOLOGY LETTERS, 2001, 205 (02) :385-389

[7] Conserved amino acid residues correlating with ketoreductase stereospecificity in modular polyketicle synthases [J].

Caffrey, P .

CHEMBIOCHEM, 2003, 4 (07) :654-657

[8]

Connor DH, 1965, Int J Lepr, V33, P698

[9] Modulation of the host immune response by a transient intracellular stage of Mycobacterium ulcerans:: the contribution of endogenous mycolactone toxin [J].

Coutanceau, E ;

Marsollier, L ;

Brosch, R ;

Perret, E ;

Goossens, P ;

Tanguy, M ;

Cole, ST ;

Small, PLC ;

Demangel, C .

CELLULAR MICROBIOLOGY, 2005, 7 (08) :1187-1196

[10] Selective suppression of dendritic cell functions by Mycobacterium ulcerans toxin mycolactone [J].

Coutanceau, Emmanuelle ;

Decalf, Jeremie ;

Martino, Angelo ;

Babon, Aurelie ;

Winter, Nathalie ;

Cole, Stewart T. ;

Albert, Matthew L. ;

Demangel, Caroline .

JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (06) :1395-1403

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