Analysis of modular bioengineered antimicrobial lanthipeptides at nanoliter scale.
Nat Chem Biol
; 15(5): 437-443, 2019 05.
Article
en En
| MEDLINE
| ID: mdl-30936500
ABSTRACT
The rise of antibiotic resistance demands the acceleration of molecular diversification strategies to inspire new chemical entities for antibiotic medicines. We report here on the large-scale engineering of ribosomally synthesized and post-translationally modified antimicrobial peptides carrying the ring-forming amino acid lanthionine. New-to-nature variants featuring distinct properties were obtained by combinatorial shuffling of peptide modules derived from 12 natural antimicrobial lanthipeptides and processing by a promiscuous post-translational modification machinery. For experimental characterization, we developed the nanoFleming, a miniaturized and parallelized high-throughput inhibition assay. On the basis of a hit set of >100 molecules, we identified variants with improved activity against pathogenic bacteria and shifted activity profiles, and extrapolated design guidelines that will simplify the identification of peptide-based anti-infectives in the future.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Péptidos
/
Sulfuros
/
Bacterias
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Ingeniería de Proteínas
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Alanina
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Antibacterianos
Idioma:
En
Revista:
Nat Chem Biol
Asunto de la revista:
BIOLOGIA
/
QUIMICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Suiza