A widespread bacterial phenazine forms S-conjugates with biogenic thiols and crosslinks proteins

Chemical Science
D HeineC Hertweck

Abstract

Phenazines are redox-active compounds produced by a range of bacteria, including many pathogens. Endowed with various biological activities, these ubiquitous N-heterocycles are well known for their ability to generate reactive oxygen species by redox cycling. Phenazines may lead to an irreversible depletion of glutathione, but a detailed mechanism has remained elusive. Furthermore, it is not understood why phenazines have so many protein targets and cause protein misfolding as well as their aggregation. Here we report the discovery of unprecedented conjugates (panphenazines A, B) of panthetheine and phenazine-1-carboxylic (PCA) acid from a Kitasatospora sp., which prompted us to investigate their biogenesis. We found that PCA reacts with diverse biogenic thiols under radical-forming conditions, which provides a plausible model for irreversible glutathione depletion. To evaluate the scope of the reaction in cells we designed biotin and rhodamine conjugates for protein labelling and examined their covalent fusion with model proteins (ketosynthase, carbonic anhydrase III, albumin). Our results reveal important, yet overlooked biological roles of phenazines and show for the first time their function in protein conjugation and cross...Continue Reading

References

Mar 10, 2001·Recent Progress in Hormone Research·P Ulrich, A Cerami
Nov 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Huimin RanGee W Lau
Mar 11, 2004·Chemical Reviews·Jane Buus Laursen, John Nielsen
Sep 21, 2004·Annual Review of Plant Biology·Klaus Apel, Heribert Hirt
Jan 20, 2006·Nature Chemical Biology·Alexa Price-WhelanDianne K Newman
Feb 16, 2006·Environmental Microbiology·Alfons J M StamsGosse Schraa
Aug 7, 2009·Chembiochem : a European Journal of Chemical Biology·Matthias MentelWulf Blankenfeldt
Nov 7, 2009·The American Journal of Pathology·Charles C CaldwellGee W Lau
Mar 25, 2010·Angewandte Chemie·Thomas BöttcherStephan A Sieber
Nov 30, 2010·Current Opinion in Chemical Biology·Jaclyn M WinterChristian Hertweck
Jan 21, 2011·Journal of the American Chemical Society·Andrea Braunshausen, Florian P Seebeck
Jul 14, 2011·Journal of the American Chemical Society·Daniel H ScharfChristian Hertweck
Jul 27, 2011·Chemical Reviews·Diego RomeroRoberto Kolter
Nov 15, 2011·ACS Chemical Biology·Julian Davies, Katherine S Ryan
Feb 18, 2012·Natural Product Reports·A CimminoR Kiss
Apr 17, 2012·Natural Product Reports·Malte GerschStephan A Sieber
Aug 7, 2012·American Journal of Respiratory Cell and Molecular Biology·Ryan C HunterDianne K Newman
Aug 14, 2012·Environmental Microbiology·Dmitri V MavrodiLinda S Thomashow
Jan 8, 2013·Journal of Bacteriology·Lars E P DietrichDianne K Newman
Sep 21, 2013·Nature·Tom BretschneiderChristian Hertweck
Feb 7, 2014·Journal of Natural Products·Marcell WagnerMarcel Jaspars
Mar 13, 2014·Journal of Natural Products·Daniel HeineChristian Hertweck
Oct 12, 2014·Neuroscience Letters·Arpita RayKim A Caldwell
Jan 20, 2015·Angewandte Chemie·Kristina V GoncharenkoFlorian P Seebeck
Mar 21, 2015·Chemico-biological Interactions·Michael Muller, Neil D Merrett
Apr 19, 2015·Trends in Biotechnology·Narendra ReddyQiuran Jiang
May 23, 2015·Chemical Communications : Chem Comm·Daniel HeineChristian Hertweck
Mar 1, 2003·The New Phytologist·Thomas F C Chin-A-WoengBen J J Lugtenberg

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Citations

Apr 19, 2017·Chemical Reviews·Kyle L DunbarChristian Hertweck

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Methods Mentioned

BETA
PCA
NMR
electrophoresis
column chromatography

Software Mentioned

Pymol

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