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La formación de enlaces dobles cis por la tioesterasa y la transferencia por la cetosintasa en la biosíntesis

Hai-Yan He¹, Man-Cheng Tang, Feng Zhang

¹State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences , 345 Lingling Road, Shanghai 200032, China.

Journal of the American Chemical Society

|March 13, 2014

Resumen

Este estudio revela nuevas funciones para los dominios de la policetida sintasa (PKS) en la biosíntesis FR901464. Un dominio tioesterasa forma enlaces cis-dobles, y un dominio cetosintasa mutado transfiere el intermedio, ofreciendo nuevos conocimientos sobre los mecanismos de la PKS.

Área de la Ciencia:

La bioquímica es la bioquímica.
Biología Molecular Biología Molecular
Química orgánica es la química orgánica.

Sus antecedentes:

Las sintasas modulares de policetido (PKS) suelen utilizar dominios de enzimas canónicas para el ensamblaje de policetido.
El sistema PKS FR901464 es inusual, ya que carece de un dominio de aciltransferasa y presenta un dominio de tioesterasa (TE) no terminal y dominios de cetosintasa (KS) mutados.

Objetivo del estudio:

Para aclarar las funciones no canónicas de los dominios TE y KS en el sistema PKS FR901464.
Para investigar el mecanismo de formación de enlaces dobles cis en la biosíntesis de policetido.

Principales métodos:

Caracterización bioquímica de los dominios de PKS.
Análisis de los intermediarios y productos de policetida.
Pruebas enzimáticas para determinar las funciones de dominio.

Principales resultados:

Se descubrió que el dominio TE no terminal cataliza la deshidratación, introduciendo un enlace doble cis en el intermedio poliquetídeo.
Se demostró que un dominio KS mutado transfiere la cadena policetídica que contiene el enlace doble cis a la proteína portadora de acilo aguas abajo.
Estas actividades representan una vía novedosa para la formación de enlaces dobles cis en el ensamblaje de policetido.

Conclusiones:

El estudio demuestra funciones enzimáticas alternativas para los dominios TE y KS más allá de sus funciones canónicas.
Estos hallazgos sugieren una nueva estrategia para generar enlaces cis-dobles en complejas estructuras poliquetídicas.
Este trabajo amplía nuestra comprensión de la versatilidad y adaptabilidad de la maquinaria PKS.

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