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Biosíntesis concisa de las papulacandinas antifúngicas
Chao Yu1, Niandi Zhang1, Jinmei Li1
1NHC Key Laboratory of Biotechnology for Microbial Drugs, State Key Laboratory of Bioactive Substance & Function of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China.
Journal of the American Chemical Society
|March 5, 2025
Resumen
Los investigadores lograron la biosíntesis completa de las papulacandinas antifúngicas utilizando la expresión heteróloga. Este avance aclara la compleja estrategia convergente de cinco componentes, incluidos los pasos enzimáticos clave para la formación del núcleo espiroketal.
Área de la Ciencia:
- La bioquímica
- Biología sintética
- Biosíntesis de productos naturales
Sus antecedentes:
- Las papulacandinas son compuestos antifúngicos con una estructura compleja.
- Comprender su biosíntesis es crucial para las aplicaciones potenciales.
Objetivo del estudio:
- Para aclarar la vía biosintética completa de las papulacandinas antifúngicas.
- Para permitir la producción heteróloga de estos valiosos compuestos.
Principales métodos:
- Expresión heteróloga del grupo de genes biosintéticos de la papulacandina.
- Pruebas enzimáticas para confirmar las funciones catalíticas.
- Análisis químico de los compuestos obtenidos.
Principales resultados:
- La biosíntesis completa se logró mediante una estrategia convergente de cinco componentes.
- Una poliquetida sintasa (PKS) fusionada con un dominio de aciltransferasa (AT) sintetiza la cadena poliquetida.
- La formación de núcleos espiroketales bencanulados tricíclicos incluye la C-glucosilación y la espirociclación catalizada por Fe (II) /α-cetoglutarato dependiente de la oxigenasa (PpcE).
Conclusiones:
- El estudio reconstruyó con éxito la vía de biosíntesis de la papulacandina en un huésped heterólogo.
- Este trabajo proporciona una base para la producción de ingeniería de papulacandinas y agentes antifúngicos relacionados.
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