Characterization and heterologous reconstitution of Taxus biosynthetic enzymes leading to baccatin III.
Science
; 383(6683): 622-629, 2024 Feb 09.
Article
en En
| MEDLINE
| ID: mdl-38271490
ABSTRACT
Paclitaxel is a well known anticancer compound. Its biosynthesis involves the formation of a highly functionalized diterpenoid core skeleton (baccatin III) and the subsequent assembly of a phenylisoserinoyl side chain. Despite intensive investigation for half a century, the complete biosynthetic pathway of baccatin III remains unknown. In this work, we identified a bifunctional cytochrome P450 enzyme [taxane oxetanase 1 (TOT1)] in Taxus mairei that catalyzes an oxidative rearrangement in paclitaxel oxetane formation, which represents a previously unknown enzyme mechanism for oxetane ring formation. We created a screening strategy based on the taxusin biosynthesis pathway and uncovered the enzyme responsible for the taxane oxidation of the C9 position (T9αH1). Finally, we artificially reconstituted a biosynthetic pathway for the production of baccatin III in tobacco.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas de Plantas
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Paclitaxel
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Taxus
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Sistema Enzimático del Citocromo P-450
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Taxoides
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Alcaloides
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Ingeniería Metabólica
Idioma:
En
Revista:
Science
Año:
2024
Tipo del documento:
Article
País de afiliación:
China