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Biosíntesis de (-) - 1S,2R) - tioester de acilo allocoronámico por una halogenasa dependiente de Fe (II) y una
Christopher S Neumann1, Christopher T Walsh
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Journal of the American Chemical Society
|October 3, 2008
Resumen
Los investigadores aclararon la biosíntesis de un nuevo aminoácido no proteinogénico, el ácido (1S,2R) -alocoronámico, utilizando el sistema de cuatro proteínas KtzABCD. Este descubrimiento abre caminos para nuevas modificaciones de péptidos.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Biosíntesis de Productos Naturales de Productos Naturales
Sus antecedentes:
- La familia kutznerida de hexapeptidolactonas contiene aminoácidos no proteígenos únicos.
- Se propone que el grupo de genes KtzABCD sea responsable de sintetizar estos aminoácidos inusuales.
Objetivo del estudio:
- Para reconstituir el sistema KtzABCD in vitro e identificar el producto final.
- Para dilucidar la vía biosintética del aminoácido no proteinogénico.
Principales métodos:
- Reconstitución in vitro del sistema KtzABCD de cuatro proteínas.
- Análisis bioquímico para identificar el producto y caracterizar los mecanismos enzimáticos.
Principales resultados:
- El sistema de cuatro proteínas fue reconstituido con éxito, dando ácido (1S,2R) -alocoronámico.
- Se demostró que la enzima KtzD (una halogenasa) y KtzA (una proteína similar a la acil-CoA deshidrogenasa) median la formación y la ciclización de un intermediario gamma-cloroisoleucil.
- El producto final se une a través de un enlace tioéster a la proteína portadora KtzC, con KtzA funcionando sin actividad redox del cofactor flavin.
Conclusiones:
- Se ha identificado un nuevo monómero, el ácido (1S,2R) -alocoronámico, y se ha aclarado su única vía de biosíntesis.
- Esta vía involucra una halogenasa no dependiente de Fe ((II) hemo y una proteína similar a la deshidrogenasa acil-CoA.
- Los hallazgos introducen un nuevo bloque de construcción para la posible incorporación en péptidos no ribosómicos.
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