Kissing Butterflies and French Fries: The phenazine biosynthesis pathway revealed
The phenazines are a group of over 100 nitrogen-containing aromatic compounds that many bacterial strains synthesize and secrete into the environment, sometimes in copious amounts. They are redox active and can reduce molecular oxygen to reactive oxygen species, explaining their broad-specificity antibiotic activity and general toxicity towards eukaryotic cells. Other functions that are currently discussed include participation in iron acquisition, in signal transduction and a role as respiratory pigments in anoxic layers of biofilm. It has also been demonstrated that they act as survival factors in infectious disease.
The first scientific report describing the isolation of the blue phenazine derivative pyocyanin from pus has been published over 150 years ago, but it was only recently that the genetic material required for phenazine biosynthesis has been identified. Phenazine biosynthesis requires genes encoded in the phz-operon, and a comparison of the available sequence data reveals that fife enzymatic activities are required to convert chorismic acid into phenazine-1-carboxylic acid, which is the common precursor of strain-specific phenazines.
In this talk I will show how we have unraveled the principal steps of phenazine biosynthesis by employing a combination of protein crystallography, synthetic organic chemistry, HPLC-coupled NMR spectroscopy and mass spectrometry. The pathway involves enzyme activities that have not been described previously, and in a broader perspective our work may show that interesting discoveries are hiding within the large number of functionally uncharacterized genes that every newly sequenced microbial genome contains.
Mentel M, Ahuja EG, Mavrodi CV, Breinbauer R, Thomshow LS, Blankenfeldt W (2009) Of Two Make One: The Biosynthesis of Phenazines. ChemBioChem 10:2295-30
Datum: 02.12.2011, 11:00
Saarbrücken, Campus UdS, E1.3, 003
Wulf Blankenfeldt, University of Bayreuth
Rolf Hartmann, DDOP