Dataset Information

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

ABSTRACT: 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??M). 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??M).

SUBMITTER: Park SR

PROVIDER: S-EPMC4757757 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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

Park Sung Ryeol SR Tripathi Ashootosh A Wu Jianfeng J Schultz Pamela J PJ Yim Isaiah I McQuade Thomas J TJ Yu Fengan F Arevang Carl-Johan CJ Mensah Abraham Y AY Tamayo-Castillo Giselle G Xi Chuanwu C Sherman David H DH

Nature communications 20160216

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 Streptomyc ...[more]

PMID: 26880271

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Dataset Information

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

Publications

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

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