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Structure elucidation and activity of kolossin A, the D-/L-Pentadecapeptide product of a giant nonribosomal peptide synthetase

Bode, Helge B. and Brachmann, Alexander O. and Jadhav, Kirtikumar B. and Seyfarth, Lydia and Dauth, Christina and Fuchs, Sebastian W. and Kaiser, Marcel and Waterfield, Nick R. and Sack, Holger and Heinemann, Stefan H. and Arndt, Hans-Dieter. (2015) Structure elucidation and activity of kolossin A, the D-/L-Pentadecapeptide product of a giant nonribosomal peptide synthetase. Angewandte Chemie, Jg. 54, Nr. 35. S. 10352-10355.

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Official URL: http://edoc.unibas.ch/dok/A6438840

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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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Kaiser, Marcel
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:Verlag Chemie
ISSN:0044-8249
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Nov 2015 10:21
Deposited On:06 Nov 2015 10:21

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