Structure Elucidation, Total Synthesis, Antibacterial In Vivo Efficacy and Biosynthesis Proposal of Myxobacterial Corramycin.
Angew Chem Int Ed Engl
; 61(51): e202210747, 2022 12 19.
Article
em En
| MEDLINE
| ID: mdl-36197755
ABSTRACT
Herein, we describe the myxobacterial natural product Corramycin isolated from Corallococcus coralloides. The linear peptide structure contains an unprecedented (2R,3S)-γ-N-methyl-ß-hydroxy-histidine moiety. Corramycin exhibits anti-Gram-negative activity against Escherichia coli (E.â
coli) and is taken up via two transporter systems, SbmA and YejABEF. Furthermore, the Corramycin biosynthetic gene cluster (BGC) was identified and a biosynthesis model was proposed involving a 12-modular non-ribosomal peptide synthetase/polyketide synthase. Bioinformatic analysis of the BGC combined with the development of a total synthesis route allowed for the elucidation of the molecule's absolute configuration. Importantly, intravenous administration of 20â
mg kg-1 of Corramycin in an E.â
coli mouse infection model resulted in 100 % survival of animals without toxic side effects. Corramycin is thus a promising starting point to develop a potent antibacterial drug against hospital-acquired infections.
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Base de dados:
MEDLINE
Assunto principal:
Escherichia coli
/
Antibacterianos
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article