title: Leader peptide and a membrane protein scaffold guide the biosynthesis of the tricyclic peptide microviridin.
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.
authors: Department of Microbiology, Institute for Biochemistry and Biology, University of Potsdam, 14476 Potsdam-Golm, Germany.
authors: Annika R
authors: AR
authors: Weiz
authors: Keishi
authors: K
authors: Ishida
authors: Katharina
authors: K
authors: Makower
authors: Nadine
authors: N
authors: Ziemert
authors: Christian
authors: C
authors: Hertweck
authors: Elke
authors: E
authors: Dittmann
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism; D000458:Cyanobacteria / Q000201:enzymology / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D008025:Ligases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010456:Peptides, Cyclic / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D021382:Protein Sorting Signals; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D010456:Peptides, Cyclic; D021382:Protein Sorting Signals; D008025:Ligases