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Information on EC 4.2.3.22 - germacradienol synthase
for references in articles please use BRENDA:EC4.2.3.22
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EC Tree 4 Lyases
4.2 Carbon-oxygen lyases
4.2.3 Acting on phosphates
4.2.3.22 germacradienol synthase
IUBMB Comments
Requires Mg2+ for activity. H-1si of farnesyl diphosphate is lost in the formation of (1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol. Formation of (-)-germacrene D involves a stereospecific 1,3-hydride shift of H-1si of farnesyl diphosphate. Both products are formed from a common intermediate . Other enzymes produce germacrene D as the sole product using a different mechanism. The enzyme mediates a key step in the biosynthesis of geosmin (see EC 4.1.99.16 geosmin synthase), a widely occurring metabolite of many streptomycetes, bacteria and fungi . Also catalyses the reaction of EC 4.2.3.75, (-)-germacrene D synthase.
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
- 4.2.3.22
- cyclases
-
meroterpenoids
- prenyltransferase
-
dmapp
- camphene
- humulene
-
copalyl
Reaction Schemes
showSynonyms
terpene cyclase, germacrene d synthase, spterp13, germacradienol/geosmin synthase, germacradienol synthase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
B7C62_00490
germacradienol synthase
germacradienol/germacrene D synthase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(2E,6E)-farnesyl diphosphate + H2O = (1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
(2E,6E)-farnesyl diphosphate + H2O = (1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
-
-
-
-
(2E,6E)-farnesyl diphosphate + H2O = (1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
catalytic mechanism via intermediate is (7R)-germacra-1(10),4-diene-11-ol
-
(2E,6E)-farnesyl diphosphate + H2O = (1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
reaction mechanism
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cyclization
additional information
additional information
putative function is as a germacradienol synthase/terpene cyclase
additional information
-
germacradienol/geosmin synthase is a bifunctional enzyme in which the N-terminal domain of the protein converts farnesyl diphosphate, while the C-terminal domain catalyzes the transformation of germacradienol to geosmin
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PATHWAY SOURCE
PATHWAYS
MetaCyc
geosmin biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
(2E,6E)-farnesyl-diphosphate diphosphate-lyase [(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol-forming]
Requires Mg2+ for activity. H-1si of farnesyl diphosphate is lost in the formation of (1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol. Formation of (-)-germacrene D involves a stereospecific 1,3-hydride shift of H-1si of farnesyl diphosphate. Both products are formed from a common intermediate [2]. Other enzymes produce germacrene D as the sole product using a different mechanism. The enzyme mediates a key step in the biosynthesis of geosmin (see EC 4.1.99.16 geosmin synthase), a widely occurring metabolite of many streptomycetes, bacteria and fungi [2]. Also catalyses the reaction of EC 4.2.3.75, (-)-germacrene D synthase.
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CAS REGISTRY NUMBER
COMMENTARY
211049-88-6
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germa-1(10),5-dien-11-ol + diphosphate
Substrates: -
Products: catalysed by the N-terminal domain of the bifunctional enzyme
Products: catalysed by the N-terminal domain of the bifunctional enzyme
?
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
2-trans,6-trans-farnesyl diphosphate + H2O
(4S,7R)-germacra-1(10)E,5E-dien-11-ol + diphosphate
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
-
Substrates: -
Products: -
Products: -
?
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
Kitasatospora albolonga YIM 101047
-
Substrates: -
Products: -
Products: -
?
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
Substrates: -
Products: -
Products: -
?
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
Substrates: -
Products: 66%
Products: 66%
?
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
Substrates: -
Products: -
Products: -
?
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
-
Substrates: enzyme is involved in geosmin biosynthesis
Products: -
Products: -
?
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
-
Substrates: enzyme is essential for geosmin biosynthesis
Products: -
Products: -
?
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
-
Substrates: cyclization reaction, mechanism of full length enzyme and N-terminal catalytic domain
Products: -
Products: -
?
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
-
Substrates: reaction is catalyzed by one of two sesquiterpene domains of the enzyme
Products: -
Products: -
?
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
Substrates: -
Products: trans-1,10-dimethyl-trans-9-decalol
Products: trans-1,10-dimethyl-trans-9-decalol
?
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
Substrates: Mg-dependent conversion
Products: -
Products: -
?
2-trans,6-trans-farnesyl diphosphate + H2O
(4S,7R)-germacra-1(10)E,5E-dien-11-ol + diphosphate
-
Substrates: key step in biosynthesis of geosmin
Products: -
Products: -
?
2-trans,6-trans-farnesyl diphosphate + H2O
(4S,7R)-germacra-1(10)E,5E-dien-11-ol + diphosphate
-
Substrates: cyclization reaction, detailed mechanism, an intermediate is (7R)-germacra-1(10),4-diene-11-ol
Products: GC-MS and NMR product configuration analysis
Products: GC-MS and NMR product configuration analysis
?
additional information
?
-
Substrates: germacradiene-11-ol synthase forms geosmin and one unknown product as side product, compound identification by GC-MS analysis
Products: -
Products: -
-
additional information
?
-
-
Substrates: stereospecificity, the 1,3-hydride shift of the (-)-germacrene D synthase of Streptomyces coelicolor A3(2) is opposite to the enzyme from Solidago canadensis
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with geranylgeranyl diphosphate
Products: -
Products: -
?
additional information
?
-
-
Substrates: catalyzes the Mg2+-dependent cyclization of conversion of farnesyl diphosphate to a mixture of germacradienol, germacrene D, and geosmin, accompanied by small amounts of octalin
Products: -
Products: -
?
additional information
?
-
Substrates: catalyze the Mg-dependent conversion of farnesyl diphosphate to the germacradienol, an essential step in the biosynthesis of geosmin
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
2-trans,6-trans-farnesyl diphosphate + H2O
(4S,7R)-germacra-1(10)E,5E-dien-11-ol + diphosphate
-
Substrates: key step in biosynthesis of geosmin
Products: -
Products: -
?
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
-
Substrates: -
Products: -
Products: -
?
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
Kitasatospora albolonga YIM 101047
-
Substrates: -
Products: -
Products: -
?
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
Substrates: -
Products: -
Products: -
?
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
Substrates: -
Products: -
Products: -
?
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
-
Substrates: enzyme is involved in geosmin biosynthesis
Products: -
Products: -
?
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
-
Substrates: enzyme is essential for geosmin biosynthesis
Products: -
Products: -
?
(2E,6E)-farnesyl diphosphate + H2O
(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
Substrates: Mg-dependent conversion
Products: -
Products: -
?
additional information
?
-
-
Substrates: catalyzes the Mg2+-dependent cyclization of conversion of farnesyl diphosphate to a mixture of germacradienol, germacrene D, and geosmin, accompanied by small amounts of octalin
Products: -
Products: -
?
additional information
?
-
Substrates: catalyze the Mg-dependent conversion of farnesyl diphosphate to the germacradienol, an essential step in the biosynthesis of geosmin
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
Cu2+
Fe2+
Mg2+
Mn2+
Zn2+
additional information
-
enzyme activity is dependent on divalent cations
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Scabies
Identification and functional analysis of genes controlling biosynthesis of 2-methylisoborneol.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000062
2-trans,6-trans-farnesyl diphosphate
-
pH 8.2, 30°C, recombinant enzyme
0.000115
2-trans,6-trans-farnesyl diphosphate
-
pH 8.2, 30°C, recombinant N-terminal domain
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3.2
2-trans,6-trans-farnesyl diphosphate
-
pH 8.2, 30°C, recombinant N-terminal domain
6.2
2-trans,6-trans-farnesyl diphosphate
-
pH 8.2, 30°C, recombinant enzyme
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8.2
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
several strains, gene cyc2 or Sco6073 encoding an enzyme with two sesquiterpene synthase domains
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
strain ATCC 27952 produces clinically important anthracycline chemotherapeutic agents of the polyketide class of antibiotics, daunorubicin and doxorubicin
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
germacradiene-11-ol synthase forms geosmin and one yet unknown product as side product
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). CYC2_STRCO
Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145)
726
0
81474
Swiss-Prot
-
A0A7H8T373_STRCX
719
0
81203
TrEMBL
other Location (Reliability: 2)
B0FLN6_STRC0
732
0
81709
TrEMBL
other Location (Reliability: 2)
Q82L49_STRAW
Streptomyces avermitilis (strain ATCC 31267 / DSM 46492 / JCM 5070 / NBRC 14893 / NCIMB 12804 / NRRL 8165 / MA-4680)
725
0
81686
TrEMBL
-
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
98000
recombinant Spterp13, consistent with the predicted mass of Spterp13 plus his-tag determined by SDS-PAGE analysis
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
the recombinant N-terminal half of the protein catalyzes the Mg2+-dependent cyclization of farnesyl diphosphate to germacradienol and germacrene D, while the highly homologous C-terminal domain catalyzes the Mg2+-dependent conversion of germacradienol to geosmin
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
expression of isolated N-terminal and C-terminal domains reveals that the N-terminal domain is responsible for the catalytic activity, while the C-terminal domain is barely active
additional information
-
construction of a cyc2 disruption mutant inactive in geosmin biosynthesis
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme from Escherichia coli strain BL21(DE3), soluble enzyme and enzyme solubilized and refolded from inclusion bodies, by ion exchange chromatography and gel filtration
-
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
construction of an ordered library of Supercos-1 clones, DNA sequence determination and analysis, subcloning in Escherichia coli
-
for construction of a geoA-deletion mutant of Streptomyces avermitilis, and for expression in Escherichia coli BL21DE3 cells
full length recombinant protein is heterologously expressed as a his-tagged fusion protein in Escherichia coli
gene SCNRRL3882_01766, codon-optimized gene, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
into the pCR2.1-TOPO vector, for functional expression full-length cDNA is sub-cloned into a pET vector
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
solubilization of recombinant enzyme from inclusion bodies by 0.02% Triton X-100 and 100 mM NaOH, and refolding
-
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
He, X.; Cane, D.E.
Mechanism and stereochemistry of the germacradienol/germacrene D synthase of Streptomyces coelicolor A3(2)
J. Am. Chem. Soc.
126
2678-2679
2004
Streptomyces coelicolor
brenda
Gust, B.; Challis, G.L.; Fowler, K.; Kieser, T.; Chater, K.F.
PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin
Proc. Natl. Acad. Sci. USA
100
1541-1546
2003
Streptomyces coelicolor
brenda
Cane, D.E.; Watt, R.M.
Expression and mechanistic analysis of a germacradienol synthase from Streptomyces coelicolor implicated in geosmin biosynthesis
Proc. Natl. Acad. Sci. USA
100
1547-1551
2003
Streptomyces coelicolor
brenda
Deguerry, F.; Pastore, L.; Wu, S.; Clark, A.; Chappell, J.; Schalk, M.
The diverse sesquiterpene profile of patchouli, Pogostemon cablin, is correlated with a limited number of sesquiterpene synthases
Arch. Biochem. Biophys.
454
123-136
2006
Pogostemon cablin (Q49SP6)
brenda
Jiang, J.; He, X.; Cane, D.E.
Geosmin biosynthesis. Streptomyces coelicolor germacradienol/germacrene D synthase converts farnesyl diphosphate to geosmin
J. Am. Chem. Soc.
128
8128-8129
2006
Streptomyces coelicolor (Q9X839), Streptomyces coelicolor
brenda
Cane, D.E.; He, X.; Kobayashi, S.; Omura, S.; Ikeda, H.
Geosmin biosynthesis in Streptomyces avermitilis. Molecular cloning, expression, and mechanistic study of the germacradienol/geosmin synthase
J. Antibiot.
59
471-479
2006
Streptomyces avermitilis (Q82L49), Streptomyces avermitilis
brenda
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
brenda
Ghimire, G.P.; Oh, T.J.; Lee, H.C.; Kim, B.G.; Sohng, J.K.
Cloning and functional characterization of the germacradienol synthase (spterp13) from Streptomyces peucetius ATCC 27952
J. Microbiol. Biotechnol.
18
1216-1220
2008
Streptomyces peucetius (B0FLN6)
brenda
Jiang, J.; He, X.; Cane, D.E.
Biosynthesis of the earthy odorant geosmin by a bifunctional Streptomyces coelicolor enzyme
Nat. Chem. Biol.
3
711-715
2007
Streptomyces coelicolor (Q9X839)
brenda
Li, G.; Zhang, Z.; Wu, M.; Chen, X.; Yin, M.; Jiang, Y.; Huang, X.; Jiang, C.; Han, L.
The discovery of germacradienol synthase Construction of genetically-engineered strain, glycosylated modification, bioactive evaluation of germacradienol
Bioorg. Chem.
124
105819
2022
Kitasatospora albolonga, Kitasatospora albolonga YIM 101047
brenda
Kracht, O.N.; Correia Cordeiro, R.S.; Hakansson, M.; Stockmann, J.; Sander, D.; Bandow, J.; Senges, C.H.R.; Logan, D.T.; Kourist, R.
Discovery of three novel sesquiterpene synthases from Streptomyces chartreusis NRRL 3882 and crystal structure of an alpha-eudesmol synthase
J. Biotechnol.
297
71-77
2019
Streptomyces chartreusis (A0A7H8T373)
brenda
EXTERNAL LINKS (specific for EC-Number 4.2.3.22)
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