Los aglicones lineales son los sustratos de la glicosiltransferasa DesVII en la biosíntesis de la metimicina:
Chai-Lin Kao1, Svetlana A Borisova, Hak Joong Kim
1Division of Medicinal Chemistry, College of Pharmacy, and Department of Chemistry and Biochemistry, University of Texas, Austin, Texas 78712, USA.
Journal of the American Chemical Society
|April 28, 2006
Resumen
Este estudio muestra que las macrolides glicosiltransferasas pueden procesar precursores lineares de policetida, no sólo los cíclicos. Esto amplía la comprensión de las vías de biosíntesis de los antibióticos macrólidos.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Síntesis de antibióticos en síntesis de antibióticos.
Sus antecedentes:
- Los antibióticos macrolidos comprenden una aglicona policetida y azúcares.
- La síntesis de agliconas está mediada por la policetida sintasa (PKS), y la glicosilación por las glicosiltransferasas.
- Se sabe que la glicosilación ocurre después de la ciclización de agliconas y la liberación de PKS.
Objetivo del estudio:
- Investigar si las macrolidoglicosiltransferasas pueden procesar precursores lineares de policetida unidos a la proteína portadora de acilo (ACP).
- Explorar una vía alternativa en la biosíntesis de antibióticos macrólidos.
Principales métodos:
- Síntesis química del precursor lineal de las agliconas, el 10-deoximetinolide, como teoestero de la N-acetilcisteamina (NAC).
- Incubación del precursor sintetizado con TDP-d-desosamina, la glucosiltransferasa DesVII y el activador DesVIII.
- Análisis del producto de reacción utilizando espectrometría de masas de alta resolución.
Principales resultados:
- Se generó un producto más polar, consistente con la glicosilación del precursor lineal.
- La glicosiltransferasa DesVII procesó con éxito el precursor lineal del 10-deoximetinolido.
- Este procesamiento se produjo con una actividad reducida pero medible en comparación con el sustrato cíclico.
Conclusiones:
- Las glicosiltransferasas macrolidas pueden reconocer y glicosilizar los precursores lineales de policetido.
- Este hallazgo amplía la especificidad conocida del sustrato de las glicosiltransferasas en la biosíntesis de macrólidos.
- El estudio proporciona nuevos conocimientos sobre la flexibilidad de las vías de ensamblaje de los antibióticos macrólidos.
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