Functional analysis of environmental DNA-derived microviridins provides new insights into the diversity of the tricyclic peptide family
- 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.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.…
Verfasserangaben: | Douglas Gatte-Picchi, Annika Weiz, Keishi Ishida, Christian Hertweck, Elke Dittmann-ThünemannORCiDGND |
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DOI: | https://doi.org/10.1128/AEM.03502-13 |
ISSN: | 0099-2240 |
ISSN: | 1098-5336 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/24334668 |
Titel des übergeordneten Werks (Englisch): | Applied and environmental microbiology |
Verlag: | American Society for Microbiology |
Verlagsort: | Washington |
Publikationstyp: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Jahr der Erstveröffentlichung: | 2014 |
Erscheinungsjahr: | 2014 |
Datum der Freischaltung: | 27.03.2017 |
Band: | 80 |
Ausgabe: | 4 |
Seitenanzahl: | 8 |
Erste Seite: | 1380 |
Letzte Seite: | 1387 |
Fördernde Institution: | National Council for Scientific and Technological Development (CNPq); German Research Foundation (DFG) [Di910/4-1, He3469/4-1] |
Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
Peer Review: | Referiert |