A Detailed View on Geosmin Biosynthesis

Abstract

The bacterial geosmin synthase is a fascinating bifunctional enzyme that has been discovered almost two decades ago. Several aspects of the cyclisation mechanism from FPP to geosmin are known, but a detailed picture of the stereochemical course of this reaction is unknown. This article reports on a deep investigation of the mechanism of geosmin synthase through isotopic labelling experiments. Furthermore, the effects of divalent cations on geosmin synthase catalysis were investigated. The addition of cyclodextrin to enzymatic reactions, a molecule that can capture terpenes, suggests that the biosynthetic intermediate (1(10)E,5E)‐germacradien‐11‐ol produced by the N‐terminal domain is passed to the C‐terminal domain not through a tunnel, but rather through release into the medium and uptake by the C‐terminal domain.

Enantioselective synthesis of all stereoisomers of geosmin and of biosynthetically related natural products

“…[23][24][25] After discovery of the geosmin synthase and its coding gene, [26][27][28][29] mechanistic investigations through in vitro conversions of various isotopically substituted farnesyl pyrophosphate (FPP) isotopomers were performed. 30,31 Taken together, this experimental work resulted in a detailed model for geosmin biosynthesis (Scheme 1). Starting from FPP, a 1,10-cyclisation to the (E,E)germacradienyl cation (A) is followed by a stereospecific deprotonation to isolepidozene (2).…”

“…Starting from FPP, a 1,10-cyclisation to the (E,E)germacradienyl cation (A) is followed by a stereospecific deprotonation to isolepidozene (2). 30 A reprotonation from the Re side at C4 31 induces ring opening to B and capture with water leads to (1(10)E,5E)-germacradien-11-ol (3), a second major product of geosmin synthase. Upon reprotonation from the Si side at C1 31 and ring closure to C a retro-Prins fragmentation leads to the octalin 4 32,33 that is again reprotonated from the Re side at C2 31 to result in D. A 1,2-hydride shift to E and capture with water ultimately yield 1.…”

“…30 A reprotonation from the Re side at C4 31 induces ring opening to B and capture with water leads to (1(10)E,5E)-germacradien-11-ol (3), a second major product of geosmin synthase. Upon reprotonation from the Si side at C1 31 and ring closure to C a retro-Prins fragmentation leads to the octalin 4 32,33 that is again reprotonated from the Re side at C2 31 to result in D. A 1,2-hydride shift to E and capture with water ultimately yield 1. A side product of geosmin biosynthesis is germacrene D (5) that is formed through a stereospecific 1,3-hydride shift 30 from A to F and deprotonation.…”

Geosmin, a Food- and Water-Deteriorating Sesquiterpenoid and Ambivalent Semiochemical, Activates Evolutionary Conserved Receptor OR11A1

“…Indeed, a geosmin production was reported to be phylogenetically conserved in genera from both bacteria and fungi . At least the microbial geosmin synthesis involves the conversion of farnesyl diphosphate to germacradienol, and further to geosmin by a sesquiterpene synthase that is encoded by a geosmin synthase gene ( geoA ) found in a variety of cyanobacteria and bacteria in both the aquatic and terrestrial environments. ,− While production of geosmin is widespread, especially in the abovementioned bacterial groups, which are found in many soils, its biological function is only partially solved and perhaps indeed diverse due to its ubiquity.…”