Total Biosynthesis of Mutaxanthene Unveils a Flavoprotein Monooxygenase Catalyzing Xanthene Ring Formation.
Angew Chem Int Ed Engl
; 62(13): e202218660, 2023 03 20.
Article
en En
| MEDLINE
| ID: mdl-36727486
Flavoprotein monooxygenases (FPMOs) play important roles in generating structural complexity and diversity in natural products biosynthesized by typeâ
II polyketide synthases (PKSs). In this study, we used genome mining to discover novel mutaxanthene analogues and investigated the biosynthesis of these aromatic polyketides and their unusual xanthene framework. We determined the complete biosynthetic pathway of mutaxathene through in vivo gene deletion and in vitro biochemical experiments. We show that a multifunctional FPMO, MtxO4, catalyzes ring rearrangement and generates the required xanthene ring through a multistep transformation. In addition, we successfully obtained all necessary enzymes for in vitro reconstitution and completed the total biosynthesis of mutaxanthene in a stepwise manner. Our results revealed the formation of a rare xanthene ring in typeâ
II polyketide biosynthesis, and demonstrate the potential of using total biosynthesis for the discovery of natural products synthesized by typeâ
II PKSs.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Productos Biológicos
/
Policétidos
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2023
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Alemania