Cryptic Isomerization in Diterpene Biosynthesis and the Restoration of an Evolutionarily Defunct P450.
J Am Chem Soc
; 145(41): 22361-22365, 2023 10 18.
Article
in En
| MEDLINE
| ID: mdl-37813821
ABSTRACT
Biosynthetic modifications of the 6/10-bicyclic hydrocarbon skeletons of the eunicellane family of diterpenoids are unknown. We explored the biosynthesis of a bacterial trans-eunicellane natural product, albireticulone A (3), and identified a novel isomerase that catalyzes cryptic isomerization in the biosynthetic pathway. We also assigned functions of two cytochromes P450 that oxidize the eunicellane skeleton, one of which was a naturally evolved non-functional P450 that, when genetically repaired, catalyzes allylic oxidation. Finally, we described the chemical susceptibility of the trans-eunicellane skeleton to undergo Cope rearrangement to yield inseparable atropisomers.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cytochrome P-450 Enzyme System
/
Diterpenes
Language:
En
Journal:
J Am Chem Soc
Year:
2023
Document type:
Article
Affiliation country:
Estados Unidos