Rhizopterin biosynthesis in Staphylococcus epidermidis

Abstract

The biosynthetic pathway from 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine (hydroxymethyldihydropteridine) to 10-formyldihydropteroic acid (dihydrorhizopterin), as found in cell-free extracts of Staphylococcus epidermidis grown in a glucose–casein hydrolysate medium, is described. In the first of at least three reactions, hydroxymethyldihydropteridine enzymatically reacts with adenosine triphosphate (ATP) in the presence of MgCl2 to form the pyrophosphate ester of this dihydropteridine and adenosine monophosphate. Cell-free enzyme preparations couple the dihydropteridine pyrophosphate with p-aminobenzoic acid (PABA) to form a phosphate containing dihydropteroic acid derivative. Enzymatic incubation of dihydropteroic acid phosphate with one-carbon donor compounds and adenosine diphosphate results in the formation of dihydrorhizopterin and ATP. Evidence is presented that the phosphorylated dihydropteroic acid compound can only be formed from the pyrophosphate ester of hydroxymethyldihydropteridine and not from dihydropteroic acid and ATP. Dihydrorhizopterin biosynthesis proceeds only from the dihydropteroic acid phosphate derivative and could not be shown to occur from 5-formyltetrahydrofolic acid. Cell-free extracts prepared from cells grown in brain heart infusion broth do not form any rhizopterin-like compounds, but form dihydropteroic acid from the phosphorylated dihydropteroic acid.