Universität zu Köln

Wirtz, Daniel A., Ludwig, Kevin C., Arts, Melina ORCID: 0000-0003-0344-6107, Marx, Carina E., Krannich, Sebastian, Barac, Paul, Kehraus, Stefan, Josten, Michaele, Henrichfreise, Beate, Mueller, Anna ORCID: 0000-0001-6420-3868, Koenig, Gabriele M., Peoples, Aaron J., Nitti, Anthony, Spoering, Amy L., Ling, Losee L., Lewis, Kim, Cruesemann, Max and Schneider, Tanja (2021). Biosynthesis and Mechanism of Action of the Cell Wall Targeting Antibiotic Hypeptin. Angew. Chem.-Int. Edit., 60 (24). S. 13579 - 13587. WEINHEIM: WILEY-V C H VERLAG GMBH. ISSN 1521-3773

Full text not available from this repository.

Abstract

Hypeptin is a cyclodepsipeptide antibiotic produced by Lysobacter sp. K5869, isolated from an environmental sample by the iChip technology, dedicated to the cultivation of previously uncultured microorganisms. Hypeptin shares structural features with teixobactin and exhibits potent activity against a broad spectrum of gram-positive pathogens. Using comprehensive in vivo and in vitro analyses, we show that hypeptin blocks bacterial cell wall biosynthesis by binding to multiple undecaprenyl pyrophosphate-containing biosynthesis intermediates, forming a stoichiometric 2:1 complex. Resistance to hypeptin did not readily develop in vitro. Analysis of the hypeptin biosynthetic gene cluster (BGC) supported a model for the synthesis of the octapeptide. Within the BGC, two hydroxylases were identified and characterized, responsible for the stereoselective beta-hydroxylation of four building blocks when bound to peptidyl carrier proteins. In vitro hydroxylation assays corroborate the biosynthetic hypothesis and lead to the proposal of a refined structure for hypeptin.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wirtz, Daniel A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ludwig, Kevin C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Arts, Melina UNSPECIFIED orcid.org/0000-0003-0344-6107 UNSPECIFIED Marx, Carina E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Krannich, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Barac, Paul UNSPECIFIED UNSPECIFIED UNSPECIFIED Kehraus, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Josten, Michaele UNSPECIFIED UNSPECIFIED UNSPECIFIED Henrichfreise, Beate UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Anna UNSPECIFIED orcid.org/0000-0001-6420-3868 UNSPECIFIED Koenig, Gabriele M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Peoples, Aaron J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nitti, Anthony UNSPECIFIED UNSPECIFIED UNSPECIFIED Spoering, Amy L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ling, Losee L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lewis, Kim UNSPECIFIED UNSPECIFIED UNSPECIFIED Cruesemann, Max UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Tanja UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-587946
DOI:	10.1002/anie.202102224
Journal or Publication Title:	Angew. Chem.-Int. Edit.
Volume:	60
Number:	24
Page Range:	S. 13579 - 13587
Date:	2021
Publisher:	WILEY-V C H VERLAG GMBH
Place of Publication:	WEINHEIM
ISSN:	1521-3773
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Chemistry, Multidisciplinary Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58794