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  -