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El clúster de genes de caliqueamicina y su tipo iterativo I enediyne PKS

Joachim Ahlert¹, Erica Shepard, Natalia Lomovskaya

¹Laboratory for Biosynthetic Chemistry, Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA.

Science (New York, N.Y.)

|August 17, 2002

Resumen

Los investigadores clonaron el grupo de genes de caliqueamicina, revelando una poliquetida sintasa (PKS) compartida esencial para la biosíntesis de enediina en las familias de cromoproteínas y no cromoproteínas.

Área de la Ciencia:

Biosíntesis de Productos Naturales Biosíntesis de Productos Naturales
Biología Molecular Biología Molecular
Genética La genética.

Sus antecedentes:

Las enediinas son una clase de potentes productos naturales con estructuras complejas.
La caliqueamicina es un antibiótico no cromoproteico bien conocido.
Las hipótesis anteriores sugirieron vías distintas para las cromoproteínas y no cromoproteínas enediynes.

Objetivo del estudio:

Clonar y caracterizar el clúster de genes biosintéticos para la caliqueamicina.
Para investigar el papel de la policetida sintasa (PKS) en la biosíntesis de enediina.
Para comparar el locus biosintético de la caliqueamicina con el de las cromoproteínas enediynes.

Principales métodos:

Clonación de genes y caracterización del locus biosintético de la caliqueamicina.
Análisis funcional de la poliquetida sintasa (PKS) dentro del grupo de genes.
Genómica comparativa de los loci biosintéticos de enediyne.

Principales resultados:

El locus biosintético completo para la caliqueamicina fue clonado y caracterizado con éxito.
Se identificó y confirmó que una inusual poliquetida sintasa (PKS) es esencial para la producción de caliqueamicina.
La PKS enediina en el locus de caliqueamicina está altamente conservada con la PKS que se encuentra en el locus de la cromoproteína enediina C-1027.

Conclusiones:

La policetida sintasa (PKS) es un componente conservado y esencial en la biosíntesis de las enediinas de cromoproteínas y no cromoproteínas.
Contrariamente a las hipótesis anteriores, las enediinas cromoproteicas y no cromoproteicas probablemente comparten caminos biosintéticos similares.
Este hallazgo proporciona nuevos conocimientos sobre la evolución y diversificación de los productos naturales enediyne.

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