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Biosíntesis del tiostreptón: prototipo de una nueva familia de bacteriocinas

Wendy L Kelly¹, Lisa Pan, Chaoxuan Li

¹School of Chemistry and Biochemistry and the Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, USA. wendy.kelly@chemistry.gatech.edu

Journal of the American Chemical Society

|March 7, 2009

Resumen

Los investigadores identificaron el prepeptido de tiostreptón (TsrA) y el grupo de genes responsable de la biosíntesis de antibióticos tiopéptidos en Streptomyces laurentii. Este estudio aclara las complejas modificaciones post-traduccionales involucradas en la producción de estos péptidos antimicrobianos.

Área de la Ciencia:

Microbiología Microbiología.
La bioquímica es la bioquímica.
Biología Molecular Biología Molecular

Sus antecedentes:

Los antibióticos tiopéptidos son metabolitos de péptidos complejos y altamente modificados con un andamio macrocíclico característico.
Su intrincada biogénesis, que involucra aminoácidos deshidratados y anillos tiazoles, ha sido mal entendida.
Las principales características estructurales incluyen anillos de deshidropiperidina/piridina y posibles sustitutos de ácido quinaldico/indolico.

Objetivo del estudio:

Para dilucidar la vía biosintética de los antibióticos tiopéptidos, específicamente el tiostreptón.
Identificar los genes y enzimas involucrados en la modificación post-traducional de los precursores del tiopéptido.
Establecer la clasificación de los tiopéptidos dentro de la familia más amplia de los péptidos antimicrobianos.

Principales métodos:

Escaneo del genoma completo de Streptomyces laurentii para identificar genes biosintéticos potenciales.
Mutagénesis génica (disrupción de tsrT) para confirmar la participación de los genes en la biosíntesis.
Análisis de metabolitos para detectar nuevos compuestos resultantes de alteraciones genéticas.
Identificación y caracterización de enzimas clave, incluyendo una amidotransferasa y una aminotransferasa.

Principales resultados:

Identificación del prepeptido de tiostrépto (TsrA) y su papel crucial en la biosíntesis.
Caracterización de un grupo de genes (tsr) responsable de la producción de tiostreptón.
La interrupción del gen tsrT condujo a la pérdida de tiostreptón y la detección de un nuevo metabolito.
La evidencia sugiere que el locus tsr codifica enzimas para la conversión del triptófano en la porción de ácido quináldico.

Conclusiones:

El estudio identificó con éxito los componentes clave de la vía biosintética del tiostreptón.
Se confirma que los tiopéptidos son bacteriocinas, péptidos antimicrobianos producidos a través de la codificación genética.
La extensa modificación post-traducional de un prepeptido es esencial para la formación de antibióticos tiopéptidos maduros.

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