Figure 3. Selected flavin-catalyzed coupling reactions.

(A) Proposed pyrrolizine ring formation by Clz9. Prechlorizidine A is dehydrogenated by Clz9-Fl_ox, followed by the regio- and stereoselective pyrrolizine-forming cyclization reaction through pyrrole coupling that affords chlorizidine A. The C8α and C6 of the flavin cofactor are likely covalently linked to His99 and Cys157 of Clz9, respectively. Oxidation of Fl_red by O₂ regenerates Fl_ox (not shown). (B) Tentative mechanism for the XiaH-catalyzed radical xiamycin coupling and oxiamycin formation. XiaH is proposed to catalyze the single-electron oxidation of the indoloterpenoid xiamycin, which then undergoes various radical dimerization reactions to bixiamycins or reacts with superoxide and possibly NAD(P)H to oxiamycin. The asterisks indicate a mixture of the respective atropoisomers with stable P- and M-configurations. (C) Proposed mechanism for C-N bond formation by the Mpy10-Mpy11 enzyme pair. Cryptic halogenation at either the C3 or the N1 positions of the monodeoxypyoluteorin monomer leads to the formation of a trihalo intermediate that undergoes nucleophilic halide displacement to yield the marinopyrrole dimer. Note that a radical mechanism is plausible too.