Biosynthetic Origin of the Hydroxamic Acid Moiety of Trichostatin A: Identification of Unprecedented Enzymatic Machinery Involved in Hydroxylamine Transfer.
J Am Chem Soc
; 139(20): 6799-6802, 2017 05 24.
Article
en En
| MEDLINE
| ID: mdl-28497964
ABSTRACT
Trichostatin A (TSA) is widely used in the field of epigenetics because it potently inhibits histone deacetylase (HDAC). In-depth studies have revealed that the hydroxamic acid group in TSA chelates the zinc(II) ion in the active site of HDAC to realize the inhibitory activity. Here we report the first identification of a complete TSA biosynthetic gene cluster from Streptomyces sp. RM72 and the heterologous production of TSA in Streptomyces albus. Biochemical analyses unambiguously demonstrate that unprecedented biosynthetic machinery catalyzes the direct transfer of hydroxylamine from a nonproteinogenic amino acid, l-glutamic acid γ-monohydroxamate, to the carboxylic acid group of trichostatic acid to form the hydroxamic acid moiety of TSA. The present study establishes the biosynthetic pathway of TSA, paving the way toward understanding the biosynthesis of other hydroxamic acid-containing natural products.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Hidroxilamina
/
Ácidos Hidroxámicos
Tipo de estudio:
Diagnostic_studies
Idioma:
En
Revista:
J Am Chem Soc
Año:
2017
Tipo del documento:
Article
País de afiliación:
Japón