Feeding of [5,5-2H2]-1-desoxy-Image -xylulose and [4,4,6,6,6-2H5]-mevalolactone to a geosmin-producing Streptomyces sp. and Fossombronia pusilla

Abstract

The biosynthesis of the trisnor sesquiterpenoid geosmin (4,8a-dimethyl-octahydro-naphthalen-4a-ol) (1) was investigated by feeding labeled [5,5-²H2]-1-desoxy-d-xylulose (11), [4,4,6,6,6-2H5]-mevalolactone (7) and [2,2-2H2]-mevalolactone (9) to Streptomyces sp. JP95 and the liverwort Fossombronia pusilla. The micro-organism produced geosmin via the 1-desoxy-d-xylulose pathway, whereas the liverwort exclusively utilized mevalolactone for terpenoid biosynthesis. Analysis of the labeling pattern in the resulting isotopomers of geosmin (1) by mass spectroscopy (EI/MS) revealed that geosmin is synthesized in both organisms by cyclization of farnesyl diphosphate to a germacradiene-type intermediate 4. Further transformations en route to geosmin (1) involve an oxidative dealkylation of an i-propyl substituent, 1,2-reduction of a resulting conjugated diene, and bicyclization of a germacatriene intermediate 13. The transformations largely resemble the biosynthesis of dehydrogeosmin (2) in cactus flowers but differ with respect to the regioselectivity of the side chain dealkylation and 1,2-reductionDeuterium labeled mevalonate and desoxy-d-xylulose fed to cultures of Streptomyces sp. JP95 (MEP pathway) and the liverwort Fossombronia pusilla (MVA pathway) are incorporated into geosmin. Both organisms produce geosmin along the same biosynthetic sequence from farnesyl diphosphate via cyclization and oxidative dealkylation of an isopropyl substituent.