A system of paired polyether epoxide hydrolases enables a mouldable enzyme for consecutive ring cyclization cascades
Toyoyuki Ose
Nature Chemistry, Published online: 16 April 2026; doi:10.1038/s41557-026-02122-9 The mechanism underlying the formation of ionophore polyethers—polyketide-derived natural products containing tetrahydrofuran and tetrahydropyran rings—has been elusive. Now structural and biochemical analyses reveal that a C26 linear precursor undergoes four successive cyclizations within the single active site of the heterodimeric polyether epoxide hydrolase MonBI·MonBII, in which MonBI promotes MonBII’s folded a