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
JF  - 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
U6  - https://doi.org/10.1128/AEM.03502-13
SN  - 0099-2240
SN  - 1098-5336
VL  - 80
IS  - 4
SP  - 1380
EP  - 1387
PB  - American Society for Microbiology
CY  - Washington
ER  - 
TY  - JOUR
A1  - Ziemert, Nadine
A1  - Ishida, Keishi
A1  - Weiz, Annika
A1  - Hertweck, Christian
A1  - Dittmann-Thünemann, Elke
T1  - Exploiting the natural diversity of microviridin gene clusters for discovery of novel tricyclic depsipeptides
N2  - Microviridins are ribosomally synthesized tricyclic depsipeptides produced by different genera of cyanobacteria. The prevalence of the microviridin gene clusters and the natural diversity of microviridin precursor sequences are currently unknown. Screening of laboratory strains and field samples of the bloom-forming freshwater cyanobacterium Microcystis via PCR revealed global occurrence of the microviridin pathway and an unexpected natural variety. We could detect 15 new variants of the precursor gene mdnA encoding microviridin backbones that differ in up to 4 amino acid positions from known isoforms of the peptide. The survey not only provides insights into the versatility of the biosynthetic enzymes in a closely related group of cyanobacteria, but also facilitates the discovery and characterization of cryptic microviridin variants. This is demonstrated for microviridin L in Microcystis aeruginosa strain NIES843 and heterologously produced variants.
Y1  - 2010
UR  - http://aem.asm.org/
U6  - https://doi.org/10.1128/AEM.02858-09
SN  - 0099-2240
ER  -