• Media type: E-Article
  • Title: Production of the Tubulin Destabilizer Disorazol in Sorangium cellulosum: Biosynthetic Machinery and Regulatory Genes
  • Contributor: Kopp, Maren; Irschik, Herbert; Pradella, Silke; Müller, Rolf
  • Published: Wiley, 2005
  • Published in: ChemBioChem, 6 (2005) 7, Seite 1277-1286
  • Language: English
  • DOI: 10.1002/cbic.200400459
  • ISSN: 1439-4227; 1439-7633
  • Keywords: Organic Chemistry ; Molecular Biology ; Molecular Medicine ; Biochemistry
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p><jats:italic>Myxobacteria show a high potential for the production of natural compounds that exhibit a wide variety of antibiotic, antifungal, and cytotoxic activities.</jats:italic><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#bib1">1</jats:ext-link>, <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#bib2">2</jats:ext-link><jats:italic> The genus</jats:italic> Sorangium <jats:italic>is of special biotechnological interest because it produces almost half of the secondary metabolites isolated from these microorganisms. We describe a transposon‐mutagenesis approach to identifying the disorazol biosynthetic gene cluster in</jats:italic> Sorangium cellulosum <jats:italic>So ce12, a producer of multiple natural products. In addition to the highly effective disorazol‐type tubulin destabilizers,</jats:italic><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#bib3">3</jats:ext-link>–<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#bib5">5</jats:ext-link> S. cellulosum <jats:italic>So ce12 produces sorangicins, potent eubacterial RNA polymerase inhibitors,</jats:italic><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#bib6">6</jats:ext-link><jats:italic> bactericidal sorangiolides, and the antifungal chivosazoles.</jats:italic><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#bib7">7</jats:ext-link>, <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#bib8">8</jats:ext-link><jats:italic> To obtain a transposon library of sufficient size suitable for the identification of the presumed biosynthetic gene clusters, an efficient transformation method was developed. We present here the first electroporation protocol for a strain of the genus</jats:italic> Sorangium<jats:italic>. The transposon library was screened for disorazol‐negative mutants. This approach led to the identification of the corresponding trans‐acyltransferase core biosynthetic gene cluster together with a region in the chromosome that is likely to be involved in disorazol biosynthesis. A third region in the genome harbors another gene that is presumed to be involved in the regulation of disorazol production. A detailed analysis of the biosynthetic and regulatory genes is presented in this paper.</jats:italic></jats:p>