Discovery, biosynthesis, and mechanism of action of the zaragozic acids: potent inhibitors of squalene synthase.
Annu Rev Microbiol
; 49: 607-39, 1995.
Article
en En
| MEDLINE
| ID: mdl-8561474
ABSTRACT
The zaragozic acids (ZAs), a family of fungal metabolites containing a novel 4,6,7-trihydroxy-2,8-dioxobicyclo[3.2.1]octane-3,4,5-tricarboxylic acid core, were discovered independently by two separate groups screening natural product sources to discover inhibitors of squalene synthase. This family of compounds all contain the same core but differ in their 1-alkyl and their 6-acyl side chains. Production of the ZAs is distributed over an extensive taxonomic range of Ascomycotina or their anamorphic states. The zaragozic acids are very potent inhibitors of squalene synthase that inhibit cholesterol synthesis and lower plasma cholesterol levels in primates. They also inhibit fungal ergosterol synthesis and are potent fungicidal compounds. The biosynthesis of the zaragozic acids appears to proceed through alkyl citrate intermediates and new members of the family have been produced through directed biosynthesis. These potent natural product based inhibitors of squalene synthase have potential to be developed either as cholesterol lowering agents and/or as antifungal agents.
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Bases de datos:
MEDLINE
Asunto principal:
Farnesil Difosfato Farnesil Transferasa
/
Ácidos Tricarboxílicos
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Compuestos Bicíclicos Heterocíclicos con Puentes
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Inhibidores Enzimáticos
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Anticolesterolemiantes
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Antifúngicos
Idioma:
En
Revista:
Annu Rev Microbiol
Año:
1995
Tipo del documento:
Article
País de afiliación:
Estados Unidos