Structure Elucidation and Activity of Kolossin A, the D‐/L‐Pentadecapeptide Product of a Giant Nonribosomal Peptide Synthetase1. Issue 35 (26th June 2015)

• Record Type: Journal Article
• Authors: Bode, Helge B.; Brachmann, Alexander O.; Jadhav, Kirtikumar B.; Seyfarth, Lydia; Dauth, Christina; Fuchs, Sebastian W.; Kaiser, Marcel; Waterfield, Nick R.; Sack, Holger; Heinemann, Stefan H.; Arndt, Hans‐Dieter
• Is Part Of: Angewandte Chemie international edition. Volume 54:Issue 35(2015)
• Page Start: 10352
• Page End: 10355
• Publication Date: 2015-06-26
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201502835
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 <italic>Photorhabdus luminescens</italic>. 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 <sc>D</sc>‐/ <sc>L</sc>‐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 <italic>Trypanosoma brucei rhodesiense</italic>, a recalcitrant parasite that causes the deadly disease African sleeping sickness.</p> </abstract>