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Enzimas que faltan en la biosíntesis del medicamento contra el cáncer vinblastina en la pervinca de Madagascar
Lorenzo Caputi1, Jakob Franke1, Scott C Farrow1
1Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
Science (New York, N.Y.)
|May 5, 2018
Resumen
Los investigadores identificaron enzimas clave en el Catharanthus roseus para la biosíntesis de la vinblastina. Este descubrimiento ayuda a comprender la diversidad química de las plantas y a desarrollar nuevas fuentes para este medicamento contra el cáncer.
Área de la Ciencia:
- Bioquímica de las plantas
- Biosíntesis de productos naturales
- Química de las plantas medicinales
Sus antecedentes:
- La vinblastina es un fármaco contra el cáncer derivado de Catharanthus roseus.
- Los rendimientos actuales de la producción son limitados, lo que requiere estrategias de abastecimiento alternativas.
- La compleja vía de biosíntesis ha obstaculizado la identificación completa del gen.
Objetivo del estudio:
- Para identificar las enzimas que faltan en la vía biosintética de la vinblastina.
- Para aclarar las transformaciones químicas que conducen a los precursores de la vinblastina.
- Para permitir la producción heteróloga de vinblastina y compuestos relacionados.
Principales métodos:
- Pruebas enzimáticas para caracterizar las actividades de la oxidasa y la reductasa.
- Análisis bioquímico de la isomerización del acetato de stemmadenina.
- Identificación y caracterización de las hidrolasas implicadas en la formación de precursores.
Principales resultados:
- Se identificaron dos enzimas clave, una oxidasa y una reductasa, que catalizan la isomerización del acetato de stemmadenina.
- Se caracterizaron dos hidrolasas, que conducen a la formación de catarantina o tabersonina.
- Se aclararon los pasos enzimáticos completos para una porción significativa de la vía de la vinblastina.
Conclusiones:
- Las enzimas identificadas completan la comprensión de una rama crítica de la biosíntesis de la vinblastina.
- Esta investigación facilita el desarrollo de sistemas de ingeniería vegetal o microbiana para la producción de vinblastina.
- Los hallazgos contribuyen a comprender la diversidad química derivada de las plantas y el descubrimiento de fármacos.
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