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Aprovechando la reversibilidad de las reacciones catalizadas por la glicosiltransferasa de productos naturales
Changsheng Zhang1, Byron R Griffith, Qiang Fu
1Laboratory for Biosynthetic Chemistry, Pharmaceutical Sciences Division, School of Pharmacy, National Cooperative Drug Discovery Group Program, University of Wisconsin (UW)-Madison, 777 Highland Avenue, Madison, WI 53705-2222, USA.
Science (New York, N.Y.)
|September 2, 2006
Resumen
Las glicosiltransferasas (GT) suelen ser unidireccionales, pero este estudio muestra que cuatro GT de las vías de la caliqueamicina y la vancomicina catalizan reacciones reversibles. Esta reversibilidad expande la diversidad de productos naturales y ayuda a crear nuevos compuestos glucosilados.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Enzimología Enzimología.
- Biosíntesis de Productos Naturales de Productos Naturales
Sus antecedentes:
- Las glucosiltransferasas (GT) son enzimas cruciales en la síntesis de carbohidratos complejos.
- Las GT se consideran tradicionalmente como enzimas que catalizan reacciones unidireccionales.
Objetivo del estudio:
- Para investigar la reversibilidad catalítica de las glicosiltransferasas.
- Explorar el potencial de los GT reversibles en la generación de diversos análogos de productos naturales.
Principales métodos:
- Ensayos enzimáticos utilizando glucosiltransferasas purificadas de las vías de la caliqueamicina y la vancomicina.
- Caracterización de los productos de reacción a través de técnicas analíticas.
Principales resultados:
- Cuatro glicosiltransferasas demostraron una catálisis fácilmente reversible, permitiendo el intercambio de azúcar y aglicón.
- Se sintetizaron más de 70 variantes glicosiladas diferencialmente de caliqueamicina y vancomicina.
- El estudio proporciona evidencia de la aplicabilidad general de la actividad de GT reversible.
Conclusiones:
- Las reacciones catalizadas por la glicosiltransferasa pueden ser reversibles, desafiando la visión tradicional unidireccional.
- Esta reversibilidad ofrece una poderosa herramienta para generar nuevos azúcares nucleótidos y diversos productos naturales.
- Los GT reversibles pueden utilizarse para la actividad enzimática in vitro en sistemas biológicos complejos.
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