1.
Angew Chem Int Ed Engl
; 56(23): 6665-6668, 2017 06 01.
Article
in English
| MEDLINE
| ID: mdl-28452105
ABSTRACT
Belactosins and cystargolides are natural product proteasome inhibitors from Actinobacteria. Both feature dipeptidic backbones and a unique ß-lactone building block. Herein, we present a detailed investigation of their biosynthesis. Identification and analysis of the corresponding gene clusters indicated that both compounds are assembled by rare single-enzyme amino acid ligases. Feeding experiments with isotope-labeled precursors and inâ vitro biochemistry showed that the formation of the ß-lactone warhead is unprecedented and reminiscent of leucine biosynthesis, and that it involves the action of isopropylmalate synthase homologues.