Biosynthesis of Sordarin Revealing a Diels-Alderase for the Formation of the Norbornene Skeleton.
Angew Chem Int Ed Engl
; 61(33): e202205577, 2022 08 15.
Article
em En
| MEDLINE
| ID: mdl-35701881
ABSTRACT
Sordarin (1) is a fungal diterpene glycoside that displays potent antifungal bioactivity through inhibition of elongation factor 2. The structures of sordarin and related compounds feature a highly rearranged tetracyclic diterpene core. In this study, we identified a concise pathway in the biosynthesis of sordarin. A diterpene cyclase (SdnA) generates the 5/8/5 cycloaraneosene framework, which is decorated by a set of P450s that catalyze a series of oxidation reactions, including hydroxylation, desaturation, and C-C bond oxidative cleavage, to give a carboxylate intermediate with a terminal alkene and a cyclopentadiene moiety. A novel Diels-Alderase SdnG catalyzes an intramolecular Diels-Alder (IMDA) reaction on this intermediate to forge the sordarin core structure. Subsequent methyl hydroxylation and glycosylation complete the biosynthesis of sordarin. Our work discloses a new strategy used by nature for the formation of the rearranged diterpene skeleton.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diterpenos
/
Indenos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article