Multiple C–C Bond Cleavage Reactions Catalyzed by Tolyporphin Tetrapyrrole Biosynthetic Enzymes

Tolyporphin A is an unusual tetrapyrrole secondary metabolite containing pendant deoxysugars and unsubstituted pyrrole β sites. Herein, we describe the biosynthesis of the tolyporphin aglycon core. HemF1 catalyzes the oxidative decarboxylation of two propionate side chains of coproporphyrinogen III, an intermediate in heme biosynthesis. HemF2 then processes the two remaining propionate groups to generate a tetravinyl intermediate. All four vinyl groups from the macrocycle are truncated by TolI via repeated C-C bond cleavages to generate the unsubstituted pyrrole β sites of tolyporphins. This study illustrates how the unprecedented C-C bond cleavage reactions branch from canonical heme biosynthesis to produce tolyporphins.