Fig. 5
Proposed mechanism of the cyclopropanation process. Upon dithionite reduction, the [4Fe-4S]2+ from the HemN-like radical SAM enzyme is converted to [4Fe-4S]+, which triggers the reductive cleavage of the first molecule of SAM1 to yield a highly reactive dAdo radical. Then, the dAdo radical abstracts a hydrogen atom from the methyl group of the second molecule of SAM2. A SAM methylene radical is thus produced and then adds to the C-11 position of the substrate 6 to generate a radical intermediate 9. The carbon-centered radical at C-12 in 9 abstracts a solvent-exchangeable proton to produce the intermediate 8. Subsequently, the His-138 residue from C10Q likely functions as a critical base and deprotonates the phenolic hydroxyl group (C-6) of 8, which induces the intramolecular SN2 cyclopropanation to yield 1 with elimination of SAH as a co-product. On the other hand, the intermediate 8 may be non-enzymatically converted to the intermediate 10 containing an exocyclic double bond via release of SAH, followed by rapid and thermodynamic driving isomerization to give a methylated off-pathway compound 7
