title: Structure Elucidation and Activity of Kolossin A, the D-/L-Pentadecapeptide Product of a Giant Nonribosomal Peptide Synthetase.
abstract: The largest continuous bacterial nonribosomal peptide synthetase discovered so far is described. It consists of 15 consecutive modules arising from an uninterrupted, fully functional gene in the entomopathogenic bacterium Photorhabdus luminescens. The identification of its cryptic biosynthesis product was achieved by using a combination of genome analysis, promoter exchange, isotopic labeling experiments, and total synthesis of a focused collection of peptide candidates. Although it belongs to the growing class of D-/ L-peptide natural products, the encoded metabolite kolossin A was found to be largely devoid of antibiotic activity and is likely involved in interspecies communication. A stereoisomer of this peculiar natural product displayed high activity against Trypanosoma brucei rhodesiense, a recalcitrant parasite that causes the deadly disease African sleeping sickness.
authors.affiliation: Merck-Stiftungsprofessur für Molekulare Biotechnologie, Goethe Universität Frankfurt, Biozentrum, Campus Riedberg 250, Max-von-Laue-Str. 9, 60438 Frankfurt/Main (Germany). h.bode@bio.uni-frankfurt.de.|Buchmann Institut für Molekulare Lebenswissenschaften (BMLS), Goethe Universität Frankfurt, Max-von-Laue-Str. 15, 60438 Frankfurt/Main (Germany). h.bode@bio.uni-frankfurt.de.
authors.forename: Helge B
authors.initials: HB
authors.lastname: Bode
authors.affiliation: Merck-Stiftungsprofessur für Molekulare Biotechnologie, Goethe Universität Frankfurt, Biozentrum, Campus Riedberg 250, Max-von-Laue-Str. 9, 60438 Frankfurt/Main (Germany).
authors.forename: Alexander O
authors.initials: AO
authors.lastname: Brachmann
authors.affiliation: Friedrich-Schiller-Universität, Institut für Organische Chemie und Makromolekulare Chemie, Humboldtstr. 10, 07743 Jena (Germany).
authors.forename: Kirtikumar B
authors.initials: KB
authors.lastname: Jadhav
authors.affiliation: Friedrich-Schiller-Universität, Institut für Organische Chemie und Makromolekulare Chemie, Humboldtstr. 10, 07743 Jena (Germany).
authors.forename: Lydia
authors.initials: L
authors.lastname: Seyfarth
authors.affiliation: Merck-Stiftungsprofessur für Molekulare Biotechnologie, Goethe Universität Frankfurt, Biozentrum, Campus Riedberg 250, Max-von-Laue-Str. 9, 60438 Frankfurt/Main (Germany).
authors.forename: Christina
authors.initials: C
authors.lastname: Dauth
authors.affiliation: Merck-Stiftungsprofessur für Molekulare Biotechnologie, Goethe Universität Frankfurt, Biozentrum, Campus Riedberg 250, Max-von-Laue-Str. 9, 60438 Frankfurt/Main (Germany).
authors.forename: Sebastian W
authors.initials: SW
authors.lastname: Fuchs
authors.affiliation: Schweizerisches Tropen- und Public-Health-Institut, Parasiten-Chemotherapie, Socinstr. 57, 4051 Basel (Switzerland).
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.affiliation: University of Warwick, Warwick Medical School, Coventry CV4 7AL (UK).
authors.forename: Nick R
authors.initials: NR
authors.lastname: Waterfield
authors.affiliation: Zentrum für Molekulare Biomedizin/Biophysik, Friedrich-Schiller-Universität Jena und Universitätsklinikum Jena, Hans-Knöll-Str. 2, 07745 Jena (Germany).
authors.forename: Holger
authors.initials: H
authors.lastname: Sack
authors.affiliation: Zentrum für Molekulare Biomedizin/Biophysik, Friedrich-Schiller-Universität Jena und Universitätsklinikum Jena, Hans-Knöll-Str. 2, 07745 Jena (Germany).
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Heinemann
authors.affiliation: Friedrich-Schiller-Universität, Institut für Organische Chemie und Makromolekulare Chemie, Humboldtstr. 10, 07743 Jena (Germany). hd.arndt@uni-jena.de.
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Arndt
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D010453:Peptide Synthases / Q000737:chemistry* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010446:Peptide Fragments; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase
keywords: biological activity; biosynthesis; natural products; peptides; total synthesis