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Probando los límites de la recodificación genética en genes esenciales

M J Lajoie¹, S Kosuri, J A Mosberg

¹Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

Science (New York, N.Y.)

|October 19, 2013

Resumen

Es factible alterar radicalmente el código genético eliminando codones raros de genes esenciales en Escherichia coli. Sin embargo, las limitaciones del diseño del genoma resaltan la necesidad de prototipos rápidos y pruebas de modificaciones del código genético.

Área de la Ciencia:

Biología sintética Biología sintética.
La ingeniería genética es la ingeniería genética.
La biotecnología microbiana.

Sus antecedentes:

La alteración radical de los códigos genéticos permite a los organismos diseñados con nuevas capacidades químicas y contención biológica.
El trabajo anterior involucró la reasignación del codón de parada UAG, pero la modificación de los codones de sentido prevalentes presenta mayores desafíos debido a sus roles regulatorios en la expresión génica.

Objetivo del estudio:

Evaluar la viabilidad de alterar radicalmente el código genético mediante la modificación de genes esenciales.
Investigar los desafíos y limitaciones asociados con la reasignación de codones en todo el genoma.

Principales métodos:

Se seleccionaron 42 genes esenciales altamente expresados en Escherichia coli para su modificación.
Se han eliminado todas las instancias de 13 codones raros de estos genes seleccionados.
Intentó mezclar todos los codones restantes a través de 80 cepas de E. coli diseñadas.

Principales resultados:

Demostró la viabilidad de la eliminación en todo el genoma de 13 codones específicos de genes esenciales.
Identificó varias restricciones de diseño del genoma que afectan el proceso de alteración del código genético.

Conclusiones:

La eliminación de codones en todo el genoma es alcanzable, pero requiere una cuidadosa consideración de las limitaciones de diseño.
Hace hincapié en la necesidad de prototipos rápidos y estrategias de pruebas iterativas para la ingeniería de modificaciones genéticas complejas.

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