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Codificación de múltiples aminoácidos no naturales a través de la evolución de un ribosoma de decodificación
Heinz Neumann1, Kaihang Wang, Lloyd Davis
1Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.
Nature
|February 16, 2010
Resumen
Los científicos diseñaron un nuevo ribosoma (ribo-Q1) para incorporar de manera eficiente múltiples aminoácidos no naturales en proteínas utilizando codones en blanco. Este avance permite la ingeniería precisa de proteínas y la creación de nuevos biomateriales.
Área de la Ciencia:
- Biología sintética Biología sintética.
- La ingeniería de proteínas es la ingeniería de proteínas.
- La bioquímica es la bioquímica.
Sus antecedentes:
- La expansión del código genético permite la modificación precisa de las propiedades de las proteínas utilizando aminoácidos de diseño.
- Los métodos actuales se limitan a la incorporación de un solo aminoácido no natural debido a la plena utilización del código genético.
Objetivo del estudio:
- Desarrollar un sistema para la incorporación eficiente de varios aminoácidos no naturales en las proteínas.
- Para crear nuevas estructuras y funciones de proteínas a través de códigos genéticos expandidos.
Principales métodos:
- Evolución sintética de un ribosoma ortogonal (ribo-Q1) para decodificar codones cuádruples y ámbar.
- Desarrollo de pares mutuamente ortogonales de aminoacil-tRNA sintetasa-tRNA para el reconocimiento específico de aminoácidos no naturales.
- Utilizando codones en blanco en el ARNm ortogonal para la incorporación dirigida de distintos aminoácidos no naturales.
Principales resultados:
- Se ha demostrado la decodificación eficiente de codones en blanco por ribo-Q1.
- Incorporó con éxito distintos aminoácidos no naturales en sitios específicos de las proteínas.
- Diseñó un enlace cruzado de proteínas específico, insensible a los redox, a través de la cicloadición bioortogonal de aminoácidos que contienen azido y alquino.
- Estableció una plataforma para codificar más de 200 combinaciones de aminoácidos no naturales.
Conclusiones:
- El sistema desarrollado supera las limitaciones de la expansión actual del código genético, permitiendo la incorporación precisa de aminoácidos múltiples no naturales.
- Esta tecnología proporciona herramientas fundamentales para la síntesis de polímeros no naturales y el avance de la evolución sintética.
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