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Diseño racional de la estereoselectividad en la clase II piruvato aldolasa BphII
Perrin Baker1, Stephen Y K Seah
1Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
Journal of the American Chemical Society
|November 16, 2011
Resumen
Los investigadores diseñaron una enzima piruvato aldolasa de clase II para crear versiones estereocomplementarias. Estas nuevas enzimas producen bloques de construcción de 4-hidroxi-2-oxoácido quiral para la síntesis orgánica.
Área de la Ciencia:
- Enzimología Enzimología.
- Química orgánica es la química orgánica.
- La biocatálisis por biocatálisis.
Sus antecedentes:
- Las aldolasas de piruvato de clase II catalizan la formación de enlaces carbono-carbono reversibles.
- La enzima BphI crea 4-hidroxi-2-oxoácidos de configuración (S).
- El residuo del sitio activo Leu-87 es crucial para la especificidad del sustrato.
Objetivo del estudio:
- Para diseñar aldolasas estereocomplementarias de piruvato de clase II.
- Para crear enzimas que produzcan 4-hidroxi-2-oxoácidos de configuración (R).
- Ampliar las herramientas biocatalíticas para la generación de síntones quirales.
Principales métodos:
- Mutagénesis dirigida al sitio de BphI en Leu-87 y Tyr-290.
- Los ensayos de actividad enzimática para la adición de aldol y la descarboxilación.
- Análisis polarimétrico para determinar la estereoquímica del producto.
Principales resultados:
- Las enzimas mutantes L87N; Y290F y L87W; Y290F mostraron actividad exclusiva con los (R) -hidroxi-2-oxoácidos.
- Las aldolasas estereocomplementarias produjeron el estereoisómero opuesto de los 4-hidroxi-2-oxoácidos.
- La eficiencia catalítica (kcat/Km) se vio mínimamente afectada en las variantes dobles.
Conclusiones:
- Las aldolasas estereocomplementarias de piruvato de clase II fueron diseñadas con éxito.
- Estas enzimas proporcionan acceso a los esqueletos quirales de 4-hidroxi-2-oxoácido (S) y (R).
- Las aldolasas diseñadas sirven como valiosos sintetones para la síntesis orgánica.
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