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Desde el triptófano a la toxina: la estrategia biosintética convergente de la naturaleza hacia la aetotonoxina

Sanjoy Adak¹, April L Lukowski¹, Rebecca J B Schäfer¹

¹Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California 92093, United States.

Journal of the American Chemical Society

|February 10, 2022

Resumen

Los investigadores descubrieron cómo el cianobacterium Aetokthonos hydrillicola produce la neurotoxina Aetokthonotoxin (AETX). Una vía de cinco enzimas convierte el triptófano en esta toxina nitrílica biindol bromada única.

Área de la Ciencia:

La bioquímica
La neurociencia
Ciencias del medio ambiente

Sus antecedentes:

Aetokthonotoxin (AETX) es una neurotoxina cianobacteriana única que causa mielinopatía vacuolar, una enfermedad neurológica fatal en las águilas calvas.
AETX es estructuralmente distinto, con un núcleo de nitrilo biindol pentabromado.

Objetivo del estudio:

Elucidar la vía de biosíntesis de la Aetokthonotoxina (AETX) en la cianobacteria de agua dulce Aetokthonos hydrillicola.
Identificar las enzimas y los mecanismos bioquímicos implicados en la síntesis de AETX.

Principales métodos:

Caracterización de las enzimas
Reconstrucción de las vías biosintéticas
Ensayos bioquímicos

Principales resultados:

Una vía de cinco enzimas convierte dos moléculas de triptófano en AETX.
La vía implica una ruta convergente con la funcionalización del monómero de indol y el acoplamiento de biarilo.
Las nuevas enzimas identificadas incluyen la triptófano halogenasa AetF y la nitrilo sintasa AetD.

Conclusiones:

La biosíntesis de AETX es un proceso complejo que involucra actividades enzimáticas únicas.
La comprensión de esta vía proporciona información sobre la producción de cianotoxina y las posibles estrategias de mitigación.

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