Discovery of a terpene synthase synthesizing a nearly non-flexible eunicellane reveals the basis of flexibility.
Nat Commun
; 15(1): 5940, 2024 Jul 15.
Article
de En
| MEDLINE
| ID: mdl-39009563
ABSTRACT
Eunicellane diterpenoids, containing a typical 6,10-bicycle, are bioactive compounds widely present in marine corals, but rarely found in bacteria and plants. The intrinsic macrocycle exhibits innate structural flexibility resulting in dynamic conformational changes. However, the mechanisms controlling flexibility remain unknown. The discovery of a terpene synthase, MicA, that is responsible for the biosynthesis of a nearly non-flexible eunicellane skeleton, enable us to propose a feasible theory about the flexibility in eunicellane structures. Parallel studies of all eunicellane synthases in nature discovered to date, including 2Z-geranylgeranyl diphosphate incubations and density functional theory-based Boltzmann population computations, reveale that a trans-fused bicycle with a 2Z-configuration alkene restricts conformational flexibility resulting in a nearly non-flexible eunicellane skeleton. The catalytic route and the enzymatic mechanism of MicA are also elucidated by labeling experiments, density functional theory calculations, structural analysis of the artificial intelligence-based MicA model, and mutational studies.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Alkyl et aryl transferases
/
Diterpènes
Langue:
En
Journal:
Nat Commun
/
Nature communications
Sujet du journal:
BIOLOGIA
/
CIENCIA
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine
Pays de publication:
Royaume-Uni