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  - 
TY  - JOUR
A1  - Weiz, Annika R.
A1  - Ishida, Keishi
A1  - Makower, Katharina
A1  - Ziemert, Nadine
A1  - Hertweck, Christian
A1  - Dittmann-Thünemann, Elke
T1  - Leader Peptide and a Membrane Protein Scaffold Guide the Biosynthesis of the Tricyclic Peptide Microviridin
JF  - Chemistry & biology
N2  - 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 omega-ester and omega-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.
Y1  - 2011
U6  - https://doi.org/10.1016/j.chembiol.2011.09.011
SN  - 1074-5521
VL  - 18
IS  - 11
SP  - 1413
EP  - 1421
PB  - Cell Press
CY  - Cambridge
ER  -