Early-stage biosynthesis of phenalinolactone diterpenoids involves sequential prenylation, epoxidation, and cyclization.
RSC Chem Biol
; 2024 Aug 05.
Article
em En
| MEDLINE
| ID: mdl-39144403
ABSTRACT
The chemical logic associated with assembly of many bacterial terpenoids remains poorly understood. We focused our efforts on the early-stage biosynthesis of the phenalinolactone diterpenoids, demonstrating that the anti/anti/syn-perhydrophenanthrene core is constructed by sequential prenylation, epoxidation, and cyclization. The functions and timing of PlaT1-PlaT3 were assigned by comprehensive heterologous reconstitution. We illustrated that the UbiA prenyltransferase PlaT3 acts on geranylgeranyl diphosphate (GGPP) in the first step of phenalinolactone biosynthesis, prior to epoxidation by the flavin-dependent monooxygenase PlaT1 and cyclization by the type II terpene cyclase PlaT2. Finally, we isolated eight new-to-nature terpenoids, expanding the scope of the bacterial terpenome. The biosynthetic strategy employed in the assembly of the phenalinolactone core, with cyclization occurring after prenylation, is rare in bacteria and resembles fungal meroterpenoid biosynthesis. The findings presented here set the stage for future discovery, engineering, and enzymology efforts in bacterial meroterpenoids.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
RSC Chem Biol
Ano de publicação:
2024
Tipo de documento:
Article