A GLYCYL RADICAL SOLUTION - OXYGEN-DEPENDENT INTERCONVERSION OF PYRUVATE FORMATE-LYASE

Pyruvate formate-lyase (PFL) catalyses the non-oxidative dissimilation of pyruvate to formate and acetyl-CoA using a radical-chemical mechan ism, The enzyme is enzymically interconverted between inactive and act ive forms, the active form contains an organic free radical located on a glycyl residue in the C-terminal portion of the polypeptide chain, Introduction of the radical into PFL only occurs anaerobically, and th e activating enzyme responsible is an iron-sulphur protein that uses S -adenosyl methionine as cofactor and reduced flavodoxin as reductant, As the radical form of PFL is inactivated by molecular oxygen it is sa feguarded during the transition to aerobiosis by conversion back to th e radical-free, oxygen-stable form, This reaction is catalysed by the anaerobically induced multimeric enzyme alcohol dehydrogenase, The gen es encoding PFL and its activating enzyme are adjacent on the chromoso me but form discrete transcriptional units. This genetic organization is highly conserved in many, but not all, organisms that have PFL, Rec ent studies have shown that proteins exhibiting significant similarity to PFL and its activating enzyme are relatively widespread in faculta tive and obligate anaerobic eubacteria, as well as archaea, The physio logical function of many of these PFL-like enzymes remains to be estab lished, It is becoming increasingly apparent that glycyl radical enzym es are more prevalent than previously surmised, They represent a class of enzymes with unusual biochemistry and probably predate the appeara nce of molecular oxygen.