HemN is a radical S-adenosyl-L-methionine (SAM) enzyme that catalyzes the oxidative decarboxylation of coproporphyrinogen III to produce protoporphyrinogen IX, an intermediate in heme biosynthesis. HemN binds two SAM molecules in the active site, but how these two SAMs are utilized for the sequential decarboxylation of the two propionate groups of coproporphyrinogen III remains largely elusive. Here we provide evidence supporting that in HemN catalysis, a SAM serves as a hydrogen relay that mediates the radical-based hydrogen transfer from the propionate to the 5ˊ-deoxyadenosyl (dAdo) radical generated from another SAM in the active site. We also observed an unexpected shunt product resulting from trapping of the SAM-based methylene radical by the vinyl moiety of the mono-decarboxylated intermediate, harderoporphyrinogen. These results require a major revision of the HemN mechanism and reveal a new paradigm of the radical-mediated hydrogen transfer in radical SAM enzymology. The corresponding author of this work is Prof. Qi Zhang. For more details, please see (Angew. Chem. Int. Ed., 2019, DOI: doi: 10.1002/anie.201814708) https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201814708.