Geosmin Biosynthesis. Mechanism of the Fragmentation−Rearrangement in the Conversion of Germacradienol to Geosmin

Geosmin ( 1 ) is responsible for the characteristic odor of moist soil. Incubation of farnesyl diphosphate ( 2, FPP) with recombinant Streptomyces coelicolor germacradienol/geosmin synthase generated geosmin ( 1 ), germacradienol ( 3 ), germacrene D ( 4 ), octalin 5, and acetone, which was trapped as 2,2-dimethylthiazolidine ( 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- 2 H 3 ]FPP ( 2a ), giving rising to the corresponding derivative of d 3 -acetone, 9a . GC−MS analysis of the labeling pattern of [6- 2 H]geosmin ( 1b ) resulting from the incubation of germacradienol/geosmin synthase with [2- 2 H]FPP ( 2b ) revealed that the H-2 proton on FPP undergoes the predicted 1,2-hydride shift to ring B of geosmin. Both sets of experimental results are consistent with a proposed mechanism of geosmin formation 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.