Chemoenzymatic synthesis of thiazolyl peptide natural products featuring an enzyme-catalyzed formal [4 + 2] cycloaddition.
J Am Chem Soc
; 137(10): 3494-7, 2015 Mar 18.
Article
en En
| MEDLINE
| ID: mdl-25742119
ABSTRACT
Thiocillins from Bacillus cereus ATCC 14579 are members of the well-known thiazolyl peptide class of natural product antibiotics, the biosynthesis of which has recently been shown to proceed via post-translational modification of ribosomally encoded precursor peptides. It has long been hypothesized that the final step of thiazolyl peptide biosynthesis involves a formal [4 + 2] cycloaddition between two dehydroalanines, a unique transformation that had eluded enzymatic characterization. Here we demonstrate that TclM, a single enzyme from the thiocillin biosynthetic pathway, catalyzes this transformation. To facilitate characterization of this new class of enzyme, we have developed a combined chemical and biological route to the complex peptide substrate, relying on chemical synthesis of a modified C-terminal fragment and coupling to a 38-residue leader peptide by means of native chemical ligation (NCL). This strategy, combined with active enzyme, provides a new chemoenzymatic route to this promising class of antibiotics.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos
/
Productos Biológicos
/
Enzimas
/
Biocatálisis
Idioma:
En
Revista:
J Am Chem Soc
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos