Identification of asm19 as an acyltransferase attaching the biologically essential ester side chain of ansamitocins using N-desmethyl-4,5-desepoxymaytansinol, not maytansinol, as its substrate.
J Am Chem Soc
; 124(23): 6544-5, 2002 Jun 12.
Article
en En
| MEDLINE
| ID: mdl-12047169
The potent antitumor activity of the ansamitocins, polyketides isolated from Actinosynnema pretiosum, is absolutely dependent on a short acyl group esterified to the C-3 oxygen of the macrolactam ring. Asm19, a gene in the ansamitocin biosynthetic gene cluster with homology to macrolide O-acyltransferase genes, is thought to encode the enzyme catalyzing this esterification. A mutant carrying an inactivated asm19 no longer produced ansamitocins but accumulated N-desmethyl-4,5-desepoxymaytansinol, rather than maytansinol, indicating that the acylation is not the terminal step of the biosynthetic sequence. Bioconversion experiments and in vitro studies with recombinant Asm19, expressed in Escherichia coli, showed that the enzyme is very specific toward its alcohol substrate, converting N-desmethyl-4,5-desepoxymaytansinol (but not maytansinol) into ansamitocins, but rather promiscuous toward its acyl substrate, utilizing acetyl-, propionyl-, butyryl-, isobutyryl-, as well as isovaleryl-CoA.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Aciltransferasas
/
Maitansina
/
Antibióticos Antineoplásicos
Tipo de estudio:
Diagnostic_studies
Idioma:
En
Revista:
J Am Chem Soc
Año:
2002
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos