title: Functional analysis of environmental DNA-derived microviridins provides new insights into the diversity of the tricyclic peptide family.
abstract: Microviridins represent a unique family of ribosomally synthesized cage-like depsipeptides from cyanobacteria with potent protease-inhibitory activities. The natural diversity of these peptides is largely unexplored. Here, we describe two methodologies that were developed to functionally characterize cryptic microviridin gene clusters from metagenomic DNA. Environmental samples were collected and enriched from cyanobacterial freshwater blooms of different geographical origins containing predominantly Microcystis sp. Microviridins were produced either directly from fosmid clones or after insertion of environmental DNA-derived gene cassettes into a minimal expression platform in Escherichia coli. Three novel microviridin variants were isolated and tested against different serine-type proteases. The comparison of the bioactivity profiles of the new congeners allows deduction of further structure-function relationships for microviridins. Moreover, this study provides new insights into microviridin processing and gene cluster organization.
authors: University of Potsdam, Institute for Biochemistry and Biology, Department of Microbiology, Potsdam-Golm, Germany.
authors: Douglas
authors: D
authors: Gatte-Picchi
authors: Annika
authors: A
authors: Weiz
authors: Keishi
authors: K
authors: Ishida
authors: Christian
authors: C
authors: Hertweck
authors: Elke
authors: E
authors: Dittmann
mesh_terms: D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D047630:Depsipeptides / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005618:Fresh Water / Q000737:chemistry / Q000382:microbiology*; D054892:Metagenome; D046931:Microcystis / Q000235:genetics / Q000254:growth & development*; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000494:pharmacology*; D017422:Sequence Analysis, DNA
chemical_list: D004269:DNA, Bacterial; D047630:Depsipeptides; D011480:Protease Inhibitors