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A novel actinomycete strain de-replication approach based on the diversity of polyketide synthase and nonribosomal peptide synthetase biosynthetic pathways
Authors:Angel Ayuso  Desmond Clark  Ignacio González  Oscar Salazar  Annaliesa Anderson  Olga Genilloud
Affiliation:(1) Centro de Investigación Básica, Merck Sharp and Dohme de España S.A., Josefa Valcárcel 38, Madrid, 28027, Spain;(2) Merck Research Laboratories, 770 Sumneytown Pike, WP16-100 , P.O. Box 4, West Point, PA 19486, USA
Abstract:The actinomycetes traditionally represent one of the most important sources for the discovery of new metabolites with biological activity; and many of these are described as being produced by polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS). We present a strain characterization system based on the metabolic potential of microbial strains by targeting these biosynthetic genes. After an initial evaluation of the existing bias derived from the PCR detection in a well defined biosynthetic systems, we developed a new fingerprinting approach based on the restriction analysis of these PKS and NRPS amplified sequences. This method was applied to study the distribution of PKS and NRPS biosynthetic systems in a collection of wild-type actinomycetes isolated from tropical soil samples that were evaluated for the production of antimicrobial activities. We discuss the application of this tool as an alternative characterization approach for actinomycetes and we comment on the relationship observed between the presence of PKS-I, PKS-II and NRPS sequences and the antimicrobial activities observed in some of the microbial groups tested.
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