RRC ID 27849
Author Weiz AR, Ishida K, Makower K, Ziemert N, Hertweck C, Dittmann E.
Title Leader peptide and a membrane protein scaffold guide the biosynthesis of the tricyclic peptide microviridin.
Journal Chem. Biol.
Abstract 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 ω-ester and ω-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.
Volume 18(11)
Pages 1413-21
Published 2011-11-23
DOI 10.1016/j.chembiol.2011.09.011
PII S1074-5521(11)00352-8
PMID 22118675
MeSH Amino Acid Motifs Amino Acid Sequence Bacterial Proteins / metabolism Cyanobacteria / enzymology Cyanobacteria / metabolism Escherichia coli / metabolism Ligases / metabolism Membrane Proteins / metabolism* Molecular Sequence Data Mutation Peptides, Cyclic / biosynthesis* Peptides, Cyclic / chemistry Peptides, Cyclic / genetics Protein Sorting Signals* Sequence Alignment
IF 6.743
Times Cited 12
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Algae NIES-843 NIES-298