TY - JOUR A1 - Gatte-Picchi, Douglas A1 - Weiz, Annika A1 - Ishida, Keishi A1 - Hertweck, Christian A1 - Dittmann-Thünemann, Elke T1 - Functional analysis of environmental DNA-derived microviridins provides new insights into the diversity of the tricyclic peptide family T2 - Applied and environmental microbiology N2 - 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. Y1 - 2014 UR - https://publishup.uni-potsdam.de/frontdoor/index/index/docId/38075 SN - 0099-2240 SN - 1098-5336 VL - 80 IS - 4 SP - 1380 EP - 1387 PB - American Society for Microbiology CY - Washington ER -