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Leader Peptide and a Membrane Protein Scaffold Guide the Biosynthesis of the Tricyclic Peptide Microviridin

  • Microviridins are unique protease inhibitors from bloom-forming cyanobacteria that have both ecological and pharmacological relevance. Their peptide backbones are produced ribosomally, and ATP grasp ligases introduce omega-ester and omega-amide bonds to yield rare cage-like structures. Bioinformatic analysis of the microviridin biosynthesis gene cluster suggests a novel type of processing machinery, which could rationalize the challenging in vivo/in vitro reconstitution of the pathway. In this work, we report the establishment of a minimal expression system for microviridins. Through bioinformatics and mutational analysis of the MdnA leader peptide we identified and characterized a strictly conserved binding motif that is specific for microviridin ligases. Furthermore, we showed that the ABC transporter MdnE is crucial for cyclization and processing of microviridins and demonstrated that MdnE is essential for stability of the microviridin biosynthesis complex.

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Author:Annika R. Weiz, Keishi Ishida, Katharina Makower, Nadine Ziemert, Christian Hertweck, Elke Dittmann-ThünemannORCiDGND
Parent Title (English):Chemistry & biology
Publisher:Cell Press
Place of publication:Cambridge
Document Type:Article
Year of first Publication:2011
Year of Completion:2011
Release Date:2017/03/26
First Page:1413
Last Page:1421
Funder:German Research Foundation [Di910/4-1]
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie
Peer Review:Referiert