Discovery of cahuitamycins as biofilm inhibitors derived from a convergent biosynthetic pathway

 

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Detalles Bibliográficos
Autores: Park, Sung Ryeol, Tripathi, Ashootosh, Wu, Jianfeng, Schultz, Pamela J., Yim, Isaiah, McQuade, Thomas J., Yu, Fengan, Arevang, Carl Johan, Mensah, Abraham Y., Tamayo Castillo, Giselle, Xi, Chuanwu, Sherman, David H.
Formato: artículo original
Fecha de Publicación:2016
Descripción:Pathogenic microorganisms often have the ability to attach to a surface, building a complex matrix where they colonize to form a biofilm. This cellular superstructure can display increased resistance to antibiotics and cause serious, persistent health problems in humans. Here we describe a high-throughput in vitro screen to identify inhibitors of Acinetobacter baumannii biofilms using a library of natural product extracts derived from marine microbes. Analysis of extracts derived from Streptomyces gandocaensis results in the discovery of three peptidic metabolites (cahuitamycins A–C), with cahuitamycin C being the most effective inhibitor (IC50=14.5 μM). Biosynthesis of cahuitamycin C proceeds via a convergent biosynthetic pathway, with one of the steps apparently being catalysed by an unlinked gene encoding a 6-methylsalicylate synthase. Efforts to assess starter unit diversification through selective mutasynthesis lead to production of unnatural analogues cahuitamycins D and E of increased potency (IC50=8.4 and 10.5 μM).
País:Kérwá
Institución:Universidad de Costa Rica
Repositorio:Kérwá
OAI Identifier:oai:https://www.kerwa.ucr.ac.cr:10669/74422
Acceso en línea:https://www.nature.com/articles/ncomms10710
https://hdl.handle.net/10669/74422
Access Level:acceso abierto
Palabra clave:Biofilms
Biosynthesis
Natural products
Peptides