Control of ß-Branching in Kalimantacin Biosynthesis: Application of 13 Câ
NMR to Polyketide Programming.
Angew Chem Int Ed Engl
; 58(36): 12446-12450, 2019 09 02.
Article
de En
| MEDLINE
| ID: mdl-31294525
ABSTRACT
The presence of ß-branches in the structure of polyketides that possess potent biological activity underpins the widespread importance of this structural feature. Kalimantacin is a polyketide antibiotic with selective activity against staphylococci, and its biosynthesis involves the unprecedented incorporation of three different and sequential ß-branching modifications. We use purified single and multi-domain enzyme components of the kalimantacin biosynthetic machinery to address inâ
vitro how the pattern of ß-branching in kalimantacin is controlled. Robust discrimination of enzyme products required the development of a generalisable assay that takes advantage of 13 Câ
NMR of a single 13 C label incorporated into key biosynthetic mimics combined with favourable dynamic properties of an acyl carrier protein. We report a previously unassigned modular enoyl-CoA hydratase (mECH) domain and the assembly of enzyme constructs and cascades that are able to generate each specific ß-branch.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Radio-isotopes du carbone
/
Spectroscopie par résonance magnétique
/
Énoyl-CoA hydratases
Langue:
En
Journal:
Angew Chem Int Ed Engl
Année:
2019
Type de document:
Article
Pays d'affiliation:
Royaume-Uni