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La estructura epoxida hidrolasa-lasalocida proporciona una visión mecánica de la biosíntesis del producto natural
Fong T Wong1, Kinya Hotta, Xi Chen
1Department of Biological Sciences, National University of Singapore , 117543 Singapore.
Journal of the American Chemical Society
|December 24, 2014
Resumen
Los investigadores aclararon el mecanismo de ciclización anti-Baldwin en la biosíntesis de productos naturales de poliéter. La estructura cristalina de la epoxida hidrolasa Lsd19 revela cómo cataliza esta reacción cinéticamente desfavorecida durante la producción de lasalocida A.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biosíntesis de Productos Naturales de Productos Naturales
- Biología Estructural Biología estructural.
Sus antecedentes:
- Los productos naturales de poliéter son moléculas complejas con diversas actividades biológicas.
- Su biosíntesis a menudo implica transformaciones químicas difíciles, como ciclizaciones cinéticamente desfavorecidas.
- La ciclización anti-Baldwin es un paso clave en la formación de éteres cíclicos en algunos productos naturales de poliéteres.
Objetivo del estudio:
- Para aclarar la base estructural y el mecanismo de la ciclización anti-Baldwin en la biosíntesis de lasalocid A.
- Para caracterizar el papel de la hidrolasa epóxido Lsd19 en este proceso.
- Proponer un mecanismo general para la selección de epoxidos por enzimas relacionadas.
Principales métodos:
- Cristalografía de rayos X para determinar la estructura de Lsd19 en complejo con lasalocid A.
- Ensayos bioquímicos para estudiar la actividad enzimática (implicado).
- Análisis estructural para inferir los mecanismos de reacción.
Principales resultados:
- Se determinó la estructura cristalina de Lsd19 complejo con lasalocid A.
- El dominio C-terminal de Lsd19 fue identificado como el dominio catalítico responsable de la ciclización anti-Baldwin.
- La estructura proporciona información sobre cómo Lsd19 selecciona y procesa su sustrato de epoxido.
Conclusiones:
- Lsd19 cataliza la ciclización anti-Baldwin, un paso crucial en la biosíntesis del lasalocida A.
- La estructura de la enzima revela el mecanismo de esta reacción cinéticamente desfavorecida.
- Basándose en estos hallazgos, se puede proponer un modelo general para la selección de epóxidos por las hidrolasas de epóxido de poliéter ionóforo.
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