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Enzyme Nomenclature
Information on EC 4.1.99.16 - geosmin synthase and Organism(s) Streptomyces coelicolor and UniProt Accession Q9X839
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4.1.99.16 geosmin synthaseIUBMB Comments
Requires Mg2+. Geosmin is the cause of the characteristic smell of moist soil. It is a bifunctional enzyme. The N-terminal part of the enzyme is EC 4.2.3.22, germacradienol synthase, and forms germacradienol from FPP. The C-terminal part of the enzyme catalyses the conversion of germacradienol to geosmin via (1S,4aS,8aS)-1,4a-dimethyl-1,2,3,4,4a,5,6,8a-octahydronaphthalene.
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Word Map
- 4.1.99.16
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odor
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geosmin-producing
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taste
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anabaena
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cyanobacterial
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isoprenoid
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sesquiterpene
- coelicolor
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off-flavors
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bloom
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freshwater
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amplicon
- circinalis
- 2-methylisoborneol
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terpenoid
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terpene
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trouble
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dolichospermum
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on-site
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aquaculture
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farnesyl
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bornet
The taxonomic range for the selected organisms is: Streptomyces coelicolor
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + H2O = (-)-geosmin + acetone
conversion of germacradienol to geosmin results in the release of the three-carbon side chain as acetone and involves a 1,2-hydride shift of the bridgehead hydrogen exclusively into ring B of geosmin
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + H2O = (-)-geosmin + acetone
the active site in the N-terminal domain of enzyme ScGS catalyzes the ionization-dependent cyclization of FPP to form diphosphate and two cyclic products: germacradienol (major product, 85%) and germacrene D (minor product, 15%). After dissociation from the N-terminal domain, germacradienol is rebound to the active site of the C-terminal domain where it is converted to geosmin in a protonation-dependent cyclization reaction accompanied by the elimination of acetone through a retro-Prins reaction. The tandem cyclization-fragmentation reactions catalyzed by ScGS require two distinct active sites, a unique alphaalpha domain architecture is predicted for ScGS based on primary structure analysis
PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
germacradienol geosmin-lyase (acetone forming)
Requires Mg2+. Geosmin is the cause of the characteristic smell of moist soil. It is a bifunctional enzyme. The N-terminal part of the enzyme is EC 4.2.3.22, germacradienol synthase, and forms germacradienol from FPP. The C-terminal part of the enzyme catalyses the conversion of germacradienol to geosmin via (1S,4aS,8aS)-1,4a-dimethyl-1,2,3,4,4a,5,6,8a-octahydronaphthalene.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + H2O
(-)-geosmin + acetone
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-
-
?
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + H2O
(-)-geosmin + acetone
catalysed by the C-terminal domain of the bifunctional enzyme
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-
?
additional information
?
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conversion of germacradienol to geosmin results in the release of the three-carbon side chain as acetone and involves a 1,2-hydride shift of the bridgehead hydrogen exclusively into ring B of geosmin
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?
additional information
?
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geosmin synthase is a bifunctional sesquiterpene synthase with alpha-alpha domain architecture that catalyzes a unique cyclization fragmentation reaction sequence
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?
additional information
?
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geosmin synthase is a bifunctional sesquiterpene synthase with alpha-alpha domain architecture that catalyzes a unique cyclization fragmentation reaction sequence
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?
additional information
?
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geosmin synthase from Streptomyces coelicolor (ScGS) catalyzes an unusual, metal-dependent terpenoid cyclization and fragmentation reaction sequence. Two distinct active sites are required for catalysis: the N-terminal domain catalyzes the ionization and cyclization of farnesyl diphosphate to form germacradienol and inorganic pyrophosphate (PPi), and the C-terminal domain catalyzes the protonation, cyclization, and fragmentation of germacradienol to form geosmin and acetone through a retro-Prins reaction. The enzyme has an alpha,alpha domain architecture, each domain contains the metal-binding motifs typical of a class I terpenoid cyclase, and each domain requires Mg2+ for catalysis. There is no direct channel for transfer of the intermediate from the active site of the N-terminal domain to that of the C-terminal domain. It is a diiffusive transfer of the germacradienol intermediate
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?
additional information
?
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geosmin synthase from Streptomyces coelicolor (ScGS) catalyzes an unusual, metal-dependent terpenoid cyclization and fragmentation reaction sequence. Two distinct active sites are required for catalysis: the N-terminal domain catalyzes the ionization and cyclization of farnesyl diphosphate to form germacradienol and inorganic pyrophosphate (PPi), and the C-terminal domain catalyzes the protonation, cyclization, and fragmentation of germacradienol to form geosmin and acetone through a retro-Prins reaction. The enzyme has an alpha,alpha domain architecture, each domain contains the metal-binding motifs typical of a class I terpenoid cyclase, and each domain requires Mg2+ for catalysis. There is no direct channel for transfer of the intermediate from the active site of the N-terminal domain to that of the C-terminal domain. It is a diiffusive transfer of the germacradienol intermediate
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + H2O
(-)-geosmin + acetone
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-
-
?
additional information
?
-
geosmin synthase is a bifunctional sesquiterpene synthase with alpha-alpha domain architecture that catalyzes a unique cyclization fragmentation reaction sequence
-
-
?
additional information
?
-
-
geosmin synthase is a bifunctional sesquiterpene synthase with alpha-alpha domain architecture that catalyzes a unique cyclization fragmentation reaction sequence
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-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
each enzyme domain requires Mg2+ for catalysis, binding structure analysis at the N-terminal domain, overview
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
C-terminal domain; germacradienol/germacrene D synthase
UniProt
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
geosmin is a powerful odorant with an extremely low human detection threshold of less than 10 parts-per-trillion, and is mainly responsible for the characteristic odor of freshly turned earth. Although geosmin contributes to the pleasant, earthy flavor of beets, it is also a commonly occurring contaminant of musty-tasting water, wine, and fish. Geosmin is not known to cause human disease, but its detection and elimination from potable water sources is a critical environmental and water quality issue
additional information
additional information
neither full-length ScGS nor constructs of the C-terminal domain can be crystallized, but homology models of the C-terminal domain are constructed based on about 36% sequence identity with the N-terminal domain, analysis of the crystal structure of the N-terminal domain in unliganded or liganded form, overview. Possible alpha,alpha domain architectures as frameworks for bifunctional catalysis
additional information
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neither full-length ScGS nor constructs of the C-terminal domain can be crystallized, but homology models of the C-terminal domain are constructed based on about 36% sequence identity with the N-terminal domain, analysis of the crystal structure of the N-terminal domain in unliganded or liganded form, overview. Possible alpha,alpha domain architectures as frameworks for bifunctional catalysis
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
geosmin synthase has alpha-alpha domain architecture. The N-terminal domain and the C-terminal domain are separated by a 41-residue linker and share 28% and 29% amino acid sequence identity, respectively, with pentalenene synthase. Each domain contains characteristic metal ion-binding motifs of class I terpenoid cyclases. The aspartate-rich motif is found as D86DHFLE91 and D455DYYP459, and the NSE/DTE motif is found as N229DLFSYQRE237 and N598DVFSYQKE606. The C-terminal domain is also predicted to adopt an alpha fold homologous to that of the N-terminal domain based on approximately 36% amino acid sequence identity between these domains. Primary, secondary and quarternary enzyme structrue analysis, and homology modeling, overview
additional information
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geosmin synthase has alpha-alpha domain architecture. The N-terminal domain and the C-terminal domain are separated by a 41-residue linker and share 28% and 29% amino acid sequence identity, respectively, with pentalenene synthase. Each domain contains characteristic metal ion-binding motifs of class I terpenoid cyclases. The aspartate-rich motif is found as D86DHFLE91 and D455DYYP459, and the NSE/DTE motif is found as N229DLFSYQRE237 and N598DVFSYQKE606. The C-terminal domain is also predicted to adopt an alpha fold homologous to that of the N-terminal domain based on approximately 36% amino acid sequence identity between these domains. Primary, secondary and quarternary enzyme structrue analysis, and homology modeling, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant N-terminal domain of ScGS, unliganded and in complex with 3 Mg2+ ions and alendronate, mixing of 600 nl of 7 mg/ml protein in 25 mM Tris, pH 8.2, 5 mM MgCl2, 10 mM BME, and 1.5 mM sodium alendronate, with 600 nl of precipitant solution containing 0.2 M sodium acetate trihydrate, pH 7.0, and 20% w/v PEG 3350, and equilibration against 0.1 ml of reservoir solution at room temperature, X-ray diffraction structure determination and analysis at 2.4 A resolution. Neither full-length ScGS nor constructs of the C-terminal domain can be crystallized, but homology models of the C-terminal domain are constructed based on about 36% sequence identity with the N-terminal domain
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant C-terminally His6-tagged full-length enzyme from Escherichia coli strain BL21(DE3)pLysS by nickel affinity chromatography, recombinant N-terminal domain of ScGS (residues 1-366) from Escherichia coli strain BL21(DE3)pLysS by ammonium sulfate fractionation, adsorption chromatography on methyl resin, gel filtration, and ultrafiltartion
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene cyc2, recombinant expression of C-terminally His6-tagged full-length enzyme and of the N-terminal domain of ScGS (residues 1-366) in Escherichia coli strain BL21(DE3)pLysS , subcloning in Escherichia coli strain XL-1 Blue
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Jiang, J.; Cane, D.E.
Geosmin biosynthesis. Mechanism of the fragmentation-rearrangement in the conversion of germacradienol to geosmin
J. Am. Chem. Soc.
130
428-429
2008
Streptomyces coelicolor (Q9X839)
Harris, G.G.; Lombardi, P.M.; Pemberton, T.A.; Matsui, T.; Weiss, T.M.; Cole, K.E.; Koeksal, M.; Murphy, F.V.; Vedula, L.S.; Chou, W.K.; Cane, D.E.; Christianson, D.W.
Structural studies of geosmin synthase, a bifunctional sesquiterpene synthase with alpha-alpha domain architecture that catalyzes a unique cyclization fragmentation reaction sequence
Biochemistry
54
7142-7155
2015
Streptomyces coelicolor (Q9X839), Streptomyces coelicolor, Streptomyces coelicolor ATCC BAA-471 / A3(2) / M145 (Q9X839)
EXTERNAL LINKS (specific for EC-Number 4.1.99.16)
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