Geosmin biosynthesis. Mechanism of the fragmentation-rearrangement in the conversion of germacradienol to geosmin

Geosmin (1) is responsible for the characteristic odor of moist sail. Incubation of famesyl diphosphate (2, FPP) with recombinant Streptomyces coelicolor germacradienol/geosmin synthese generetes geosmin (1), germacradienol (3), germacrene D (4), octatin 5, and acetone, which was trapped as 2,2-dimethylthiamzolidine (9) by reaction with cysteamine. The acetone was shown to be derived by fragmentation of the 2-hydroxypropyl moiety of germacradienol by incubation with [13.13,13-H-2(3)]FPP (2a). giving rising to the corresponding derivative of d(3)-acetone, 9a. GC-MS analysis of the labeling pattern of [6-H-2]geosmin (1b) resulting from the incubation of germacradienol/geosmin synthase with [2-H-2]FPP (2b) revealed that the H-2 proton on FPP underyoes the predicted 1.2-hydride shift to ring B of geosmin. Both sets of experimental results are consistent with a proposed mechanism of geosmin fomation involving protonation-cyclization of germacradienol with loss of the 2-hydroxypropyl moiety as acetone by a retro-Prins fragmentation to give octalin intermediate 5, followed by protonation of 5, 1,2-hydride shift. and capture of water.