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La reutilización de las hidroxilasas de hierro no hemo para permitir la instalación de nitrilo catalítico a través de
Madison Davidson1, Meredith McNamee1, Ruixi Fan2
1Department of Chemistry , North Carolina State University , Raleigh , North Carolina 27695 , United States.
Journal of the American Chemical Society
|February 14, 2019
Resumen
Las enzimas de hierro pueden redirigirse para formar nitriles en lugar de hidroxilos mediante la introducción de un grupo azido. Este descubrimiento expande las capacidades catalíticas del hierro no hemo y las enzimas dependientes del 2-oxoglutarato.
Área de la Ciencia:
- La bioquímica
- Enzimología
- Química orgánica
Sus antecedentes:
- Las enzimas dependientes del hierro no hemo y del 2-oxoglutarato (Fe/2OG) catalizan las reacciones de hidroxilación.
- Las enzimas previamente identificadas incluyen l-Ile 4-hidroxilasa, l-Leu 5-hidroxilasa y polioxina dihidroxilasa.
Objetivo del estudio:
- Investigar el alcance del sustrato de las hidroxilasas Fe/2OG con isómeros de leucina.
- Demostrar la redirección de la actividad catalítica de la enzima Fe/2OG mediante la modificación del sustrato.
- Para explorar nuevas transformaciones enzimáticas más allá de la hidroxilación canónica.
Principales métodos:
- Ensayos enzimáticos con isómeros de leucina y sustratos modificados.
- Caracterización de los productos de reacción para determinar la especificidad de la región e identificar nuevas transformaciones.
- Estudios mecánicos relacionados con la activación del enlace C-H y la formación de nitrilo dirigida por el grupo azido.
Principales resultados:
- Las hidroxilasas Fe/2OG acomodan isómeros de leucina, catalizando la hidroxilación regiospecífica.
- La introducción de un grupo azido redirige las enzimas para instalar un grupo nitrilo en lugar de un grupo hidroxilo.
- La reacción procede a través de la activación del enlace C-H por una especie Fe (IV) -oxo, seguida de la formación de enlaces CN dirigidos por azido.
Conclusiones:
- Las enzimas Fe/2OG exhiben una aceptación de sustrato y una versatilidad catalítica más amplias que las conocidas anteriormente.
- La ingeniería asistida por sustrato puede redirigir las enzimas Fe/2OG para realizar reacciones no nativas como la instalación de nitrilo.
- Este estudio abre nuevas vías para ampliar el repertorio sintético de las enzimas Fe/2OG.
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