Andreas Hornung1, Marcelo Bertazzo2, Agnieszka Dziarnowski1, Kathrin Schneider2, Katrin Welzel1, Sven‐Eric Wohlert1, MEIKE HOLZENKÄMPFER1, Graeme Nicholson3, Andreas Bechthold4, Roderich D. Süßmuth2, Andreas Vente1, Stefan Pelzer1
1Combinature Biopharm AG, Robert‐Roessle‐Strasse 10, 13125 Berlin, Germany, Fax: (+49) 30‐94894051
2Technische Universität Berlin, Institut für Chemie, Strasse des 17. Juni 124, 10623 Berlin, Germany
3Eberhard‐Karls‐Universität Tübingen, Institut für Organische Chemie, Auf der Morgenstelle 18, 72076 Tübingen, Germany
4Albert-Ludwigs-Universität Freiburg, Institut für Pharmazeutische Wissenschaften, Pharmazeutische Biologie und Biotechnologie, Stefan-Meier-Strasse 19, 79104 Freiburg, Germany
Tóm tắt
AbstractThe potential of actinomycetes to produce natural products has been exploited for decades. Recent genomic sequence analyses have revealed a previously unrecognized biosynthetic potential and diversity. In order to rationally exploit this potential, we have developed a sequence‐guided genetic screening strategy. In this “genome mining” approach, genes that encode tailoring enzymes from natural product biosyntheses pathways serve as indicator genes for the identification of strains that have the genetic potential to produce natural products of interest. We chose halogenases, which are known to be involved in the synthesis of halometabolites as representative examples. From PCR screening of 550 randomly selected actinomycetes strains, we identified 103 novel putative halogenase genes. A phylogenetic analysis of the corresponding putative halogenases, and the determination of their sequential context with mass spectrometric analysis of cultures filtrates revealed a distinct correlation between the sequence and secondary metabolite class of the halometabolite. The described screening strategy allows rapid access to novel natural products with predetermined structural properties.
