Fig. 1
Pleuromutilin commercial derivatives and proposed cyclisation mechanism. a Structure of pleuromutilin and its commercial derivatives. b Outline of cyclisation to the pleuromutilin tricyclic scaffold, as reported by Arigoni4, 5 and Birch et al.6. The class II terpene synthase domain of Pl-Cyc promotes ring contraction during the protonation-dependent cyclisation of GGPP. The class I terpene synthase domain then catalyses formation of the 8-membered ring through ionisation-dependent dephosphorylation. Trapping with water introduces the first hydroxy group of the molecule at C-14 of the tricyclic scaffold
