Send to

Choose Destination
Angew Chem Int Ed Engl. 2019 Mar 18. doi: 10.1002/anie.201814708. [Epub ahead of print]

Revisiting the Mechanism of the Anaerobic Coproporphyrinogen III Oxidase HemN.

Author information

Department of Chemistry, Fudan University, Shanghai, 200433, China.
State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.


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. Provided here is evidence showing that in HemN catalysis a SAM serves as a hydrogen relay which mediates a radical-based hydrogen transfer from the propionate to the 5'-deoxyadenosyl (dAdo) radical generated from another SAM in the active site. Also observed was 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 suggest a major revision of the HemN mechanism and reveal a new paradigm of the radical-mediated hydrogen transfer in radical SAM enzymology.


biosynthesis; enzymes; heme; radicals; reaction mechanisms


Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center