Un grupo de genes que contiene dos poliquetidas sintasas fúngicas codifica la vía biosintética para un poliquetido, la asperfurana, en el Aspergillus nidulans
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Yi-Ming Chiang1, Edyta Szewczyk, Ashley D Davidson
1Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, California 90089, USA.
Journal of the American Chemical Society
|February 10, 2009
Resumen
La minería genómica en Aspergillus nidulans descubrió un cúmulo de genes crípticos que producen un nuevo policetido, la asperfuranona. Este descubrimiento pone de relieve el potencial para encontrar nuevos productos naturales en hongos bien estudiados.
Área de la Ciencia:
- La micología de la micología.
- La bioquímica es la bioquímica.
- La genómica es la genómica.
Sus antecedentes:
- La secuenciación del genoma de las especies de Aspergillus revela muchas vías de metabolismo secundario no caracterizadas.
- Aspergillus nidulans posee 27 poliquetidas sintasas (PKS), incluida una PKS altamente reducida (HR-PKS) y una PKS no reducida (NR-PKS) ubicada adyacente.
- No se conocían los productos de estos genes específicos de PKS, lo que sugiere un clúster de genes crípticos para un producto natural desconocido.
Objetivo del estudio:
- Para investigar un cúmulo de genes crípticos en Aspergillus nidulans que contiene dos genes PKS adyacentes.
- Para identificar y caracterizar el nuevo producto natural producido por este grupo de genes.
- Para dilucidar la vía biosintética del compuesto recién descubierto.
Principales métodos:
- Análisis bioinformático del genoma de Aspergillus nidulans para identificar los genes de PKS.
- Manipulación genética, incluida la sustitución del promotor de un activador transcripcional putativo (homólogo al CtnR) por un promotor inducible (alcA).
- Estudios de deleción de genes para confirmar los genes involucrados en la vía biosintética.
- Análisis químico para identificar el nuevo producto de policetida.
Principales resultados:
- Se produjo con éxito un nuevo policetido, llamado asperfuranona, mediante la inducción del cúmulo de genes crípticos.
- Se confirmó que la vía de biosíntesis de la asperfuranona involucra los dos genes PKS adyacentes y cinco genes adicionales.
- Se estableció una vía biosintética propuesta para la asperfuranona basada en experimentos de deleción génica.
Conclusiones:
- El estudio identificó con éxito un nuevo policetido, la asperfuranona, de un grupo de genes no caracterizado previamente en Aspergillus nidulans.
- Los enfoques de minería genómica son efectivos para descubrir nuevos productos naturales, incluso en organismos bien estudiados.
- Los hallazgos amplían nuestra comprensión del metabolismo secundario de los hongos y proporcionan una base para futuras investigaciones sobre las propiedades y aplicaciones de la asperfuranona.
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