Total Synthesis of the Nonribosomal Peptide Surugamideâ
B and Identification of a New Offloading Cyclase Family.
Angew Chem Int Ed Engl
; 57(30): 9447-9451, 2018 07 20.
Article
em En
| MEDLINE
| ID: mdl-29808953
ABSTRACT
The cathepsinâ
B inhibitor surugamideâ
B (2), along with structurally related derivatives (A and C-E), has previously been isolated from the marine actinomycete Streptomyces sp. JAMM992. The biosynthetic genes are unexpectedly part of a cluster of four non-ribosomal peptide synthetase (NRPS) genes, two of which are responsible for the biosynthesis of the additional linear decapeptide surugamideâ
F. However, the thioesterase domain required for the later stage of the biosynthesis of the cyclic peptides surugamidesâ
A-E is not present in any module architecture of the surugamide NRPSs. Herein, we report the first total synthesis of surugamideâ
B (2) through the macrocyclization at the biomimetic position, which not only alleviated the Cα epimerization in the macrolactamization process, but also efficiently provided 2 in 34 % yield for 18 steps. Furthermore, both the chemical and enzymatic studies with the biosynthetic precursor mimics revealed that the stand-alone enzyme SurE, which belongs to the penicillin-binding protein family, is responsible for macrocyclization of the tethered octapeptidyl intermediate.
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Base de dados:
MEDLINE
Assunto principal:
Adenilil Ciclases
/
Compostos Macrocíclicos
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article