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From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
Los intercambios de dominio racionales descifran la programación en las sintasas poliquetidas altamente reductoras de
Katja M Fisch1, Walid Bakeer, Ahmed A Yakasai
1School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, UK.
Journal of the American Chemical Society
|September 9, 2011
Resumen
La comprensión de la programación de las sintetasas poliquetidas iterativas (PKS) es crucial. Los intercambios de dominios en PKS revelaron los orígenes de la programación y permitieron la resurrección del extinto metabolito bassianin.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Ingeniería Metabólica Ingeniería Metabólica.
Sus antecedentes:
- Las sintetasas policetidas altamente reductoras iterativas (PKS) son clave en el metabolismo secundario.
- El mecanismo de programación de estos PKS sigue siendo en gran medida desconocido.
- La tenelina y la desmetilbassianina están estrechamente relacionadas con los metabolitos de las policetidas.
Objetivo del estudio:
- Para dilucidar el mecanismo de programación de la reducción altamente iterativa PKS.
- Investigar el papel de dominios específicos en la función del PKS.
- Para reprogramar la PKS para la producción de metabolitos nuevos o extintos.
Principales métodos:
- Intercambios racionales de dominio entre tenelina y desmetilbassianina en el PKS.
- Expresión de PKS híbrido diseñado en Aspergillus oryzae.
- Coexpresión de genes específicos del citocromo P450.
Principales resultados:
- Se produjeron compuestos reprogramados con patrones de metilación y longitudes de cadena alterados.
- Los intercambios de dominios se asignaron directamente a los cambios en la formación del producto.
- La resurrección del extinto metabolito bassianina se logró a través de intercambios de dominio y la coexpresión de P450.
Conclusiones:
- Este estudio revela el origen de la programación en sistemas PKS iterativos.
- Los intercambios de dominios proporcionan una poderosa herramienta para la comprensión y la ingeniería de PKS.
- La resurrección de la bassianina demuestra el potencial para descubrir nuevos productos naturales.
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