Polyether Cyclization Cascade Alterations in Response to Monensin Polyketide Synthase Mutations.
Chembiochem
; 23(2): e202100584, 2022 01 19.
Article
en En
| MEDLINE
| ID: mdl-34729883
The targeted manipulation of polyketide synthases has in recent years led to numerous new-to-nature polyketides. For typeâ
I polyketide synthases the response of post-polyketide synthases (PKS) processing enzymes onto the most frequently polyketide backbone manipulations is so far insufficiently studied. In particular, complex processes such as the polyether cyclisation in the biosynthesis of ionophores such as monensin pose interesting objects of research. We present here a study of the substrate promiscuity of the polyether cyclisation cascade enzymes in monensin biosynthesis in the conversion of redox derivatives of the nascent polyketide chain. LC-HRMS/MS2 -based studies revealed a remarkable flexibility of the post-PKS enzymes. They acted on derivatized polyketide backbones based on the three possible polyketide redox states within two different modules and gave rise to an altered polyether structure. One of these monensin derivatives was isolated and characterized by 2D-NMR spectroscopy, crystallography, and bioactivity studies.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Monensina
/
Mutación Puntual
/
Sintasas Poliquetidas
/
Éteres
Idioma:
En
Revista:
Chembiochem
Asunto de la revista:
BIOQUIMICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Alemania