Eukaryotes and gram-negative bacteria share the canonical pathway (blue). Gram-positive bacteria (purple) and denitrifying/sulfate reducing bacteria and archaea (orange) have distinct pathways that branch off following the coproporphyrinogen III (copro’gen) intermediate. The oxidation of porphyrinogens can use O2 as a 2e-/2H+ acceptor, generating H2O2 as a byproduct (i.e., steps catalyzed by CgdC, PgoX); alternatively, NAD(P)+ can serve as a 2e-/H+ acceptor in the presence of an active site acid (PgdH1, PgdH2). CgdH is a radical SAM-dependent enzyme. The electron acceptors for CgdH and CgoX have not been experimentally verified.