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La maduración de tiostreptón que implica una forma de desesterificación-amidación para procesar la columna vertebral
1State Key Laboratory of Bioorganic 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
|February 18, 2011
Resumen
Este estudio revela una nueva vía de desesterificación-amidación en la maduración del tiostreptón. Este proceso genera la amida terminal, descubriendo una metilación críptica C-terminal en la biosíntesis del tiopéptido.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Microbiología Microbiología.
Sus antecedentes:
- Los tiopéptidos son una clase de antibióticos peptídicos complejos y modificados con relevancia clínica.
- Su biosíntesis implica una formación de núcleo conservada, pero pasos de adaptación únicos para los miembros individuales.
Objetivo del estudio:
- Para dilucidar el inusual proceso de desesterificación-amidación en la maduración del antibiótico tiopéptido thiostrepton.
- Para identificar las enzimas e intermedios involucrados en la generación de la fracción de amida terminal.
Principales métodos:
- Ensayos enzimáticos utilizando proteínas purificadas TsrB y TsrC.
- Análisis de los intermediarios de reacción en la biosíntesis del tiostreptón.
- Caracterización bioquímica de las etapas de desesterificación y amidación.
Principales resultados:
- TsrB identificado como una carboxilesterasa que cataliza la hidrólisis del éster metílico a un intermediario carboxilato.
- Se demostró que TsrC, una amidotransferasa, convierte el carboxilato en la amida terminal.
- Reveló una metilación críptica C-terminal del péptido precursor.
Conclusiones:
- Los hallazgos revelan una nueva vía de desesterificación-amidación crítica para la estructura final del tiostreptón.
- Esta vía pone de relieve un mecanismo potencialmente extendido para generar diversas modificaciones C-terminales (ester, carboxilato, amida) en la biosíntesis del tiopéptido.
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