Discovery of Thanafactin A, a Linear, Proline-Containing Octalipopeptide from Pseudomonas sp. SH-C52, Motivated by Genome Mining
- Norbert KirchnerNorbert KirchnerPharmaceutical Institute, Department of Pharmaceutical Biology, University of Tübingen, 72076 Tübingen, GermanyMore by Norbert Kirchner,
- Carolina Cano-PrietoCarolina Cano-PrietoPharmaceutical Institute, Department of Pharmaceutical Biology, University of Tübingen, 72076 Tübingen, GermanyMore by Carolina Cano-Prieto,
- Anna-Christina Schulz-FinckeAnna-Christina Schulz-FinckePharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn, 53121 Bonn, GermanyMore by Anna-Christina Schulz-Fincke,
- Michael GütschowMichael GütschowPharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn, 53121 Bonn, GermanyMore by Michael Gütschow,
- Nico OrtliebNico OrtliebDepartment of Microbiology and Biotechnology, Interfaculty Institute of Microbiology and Infection Medicine, Eberhard Karls University Tübingen, 72076 Tübingen, GermanyGerman Centre for Infection Research (DZIF), Partner Site Tübingen, 72076 Tübingen, GermanyMore by Nico Ortlieb,
- Julia MoschnyJulia MoschnyDepartment of Microbiology and Biotechnology, Interfaculty Institute of Microbiology and Infection Medicine, Eberhard Karls University Tübingen, 72076 Tübingen, GermanyMore by Julia Moschny,
- Timo H. J. NiedermeyerTimo H. J. NiedermeyerDepartment of Microbiology and Biotechnology, Interfaculty Institute of Microbiology and Infection Medicine, Eberhard Karls University Tübingen, 72076 Tübingen, GermanyGerman Centre for Infection Research (DZIF), Partner Site Tübingen, 72076 Tübingen, GermanyMore by Timo H. J. Niedermeyer,
- Jeannie HorakJeannie HorakPharmaceutical Institute, Department of Pharmaceutical Analysis and Bioanalysis, University of Tübingen, 72076 Tübingen, GermanyDr. von Hauner Children’s Hospital, Department of Metabolic and Nutritional Medicine, University of Munich Medical Center, Campus Innenstadt, 80337 Muenchen, GermanyMore by Jeannie Horak,
- Michael LämmerhoferMichael LämmerhoferPharmaceutical Institute, Department of Pharmaceutical Analysis and Bioanalysis, University of Tübingen, 72076 Tübingen, GermanyMore by Michael Lämmerhofer,
- Menno van der VoortMenno van der VoortLaboratory of Phytopathology, Wageningen University, Wageningen, NetherlandsMore by Menno van der Voort,
- Jos M. RaaijmakersJos M. RaaijmakersDepartment of Microbial Ecology, Netherlands Institute of Ecology (NIOO-KNAW), Wageningen, The NetherlandsInstitute of Biology, Leiden University, Leiden, The NetherlandsMore by Jos M. Raaijmakers, and
- Harald Gross*Harald Gross*Tel: +49-7071-2976970. Fax: +49-7071-295250. E-mail: [email protected]Pharmaceutical Institute, Department of Pharmaceutical Biology, University of Tübingen, 72076 Tübingen, GermanyGerman Centre for Infection Research (DZIF), Partner Site Tübingen, 72076 Tübingen, GermanyMore by Harald Gross
Abstract

Genome mining of the bacterial strains Pseudomonas sp. SH-C52 and Pseudomonas fluorescens DSM 11579 showed that both strains contained a highly similar gene cluster encoding an octamodular nonribosomal peptide synthetase (NRPS) system which was not associated with a known secondary metabolite. Insertional mutagenesis of an NRPS component followed by comparative profiling led to the discovery of the corresponding novel linear octalipopeptide thanafactin A, which was subsequently isolated and its structure determined by two-dimensional NMR and further spectroscopic and chromatographic methods. In bioassays, thanafactin A exhibited weak protease inhibitory activity and was found to modulate swarming motility in a strain-specific manner.
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