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Information on EC 5.4.99.41 - lupeol synthase and Organism(s) Arabidopsis thaliana and UniProt Accession Q9C5M3
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5.4.99.41 lupeol synthaseIUBMB Comments
Also forms some beta-amyrin. The recombinant enzyme from Arabidopsis thaliana gives a 1:1 mixture of lupeol and lupan-3beta,20-diol with small amounts of beta-amyrin, germanicol, taraxasterol and psi-taraxasterol. See EC 4.2.1.128 (lupan-3beta,20-diol synthase).
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Word Map
- 5.4.99.41
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triterpene
-
triterpenoids
- cycloartenol
- cyclases
- beta-amyrin
-
pentacyclic
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betulinic
-
oleanolic
-
epoxidase
- mangrove
- glycyrrhizin
- lanosterol
- taraxacum
- phytosterols
- dandelion
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oleanane
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kandelia
- glabra
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oleanane-type
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soyasaponins
- taraxerol
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bglus
- rhizophoraceae
- candel
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bruguiera
- gymnorrhiza
The taxonomic range for the selected organisms is: Arabidopsis thaliana
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
lupeol synthase, rclus, mdosc5, atlup1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(3S)-2,3-epoxy-2,3-dihydrosqualene = lupeol
the final proton abstraction takes place from either of the two gem-dimethyl groups in a 1:1 ratio
(3S)-2,3-epoxy-2,3-dihydrosqualene = lupeol
the C17 configuration of the tetracyclic intermediate dammarenyl cation can be deduced from the angular methyl configuration of the pentacyclic or 6-6-6-6 tetracyclic product
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PATHWAY SOURCE
PATHWAYS
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-, -, -
SYSTEMATIC NAME
IUBMB Comments
(3S)-2,3-epoxy-2,3-dihydrosqualene mutase (cyclizing, lupeol-forming)
Also forms some beta-amyrin. The recombinant enzyme from Arabidopsis thaliana [3] gives a 1:1 mixture of lupeol and lupan-3beta,20-diol with small amounts of beta-amyrin, germanicol, taraxasterol and psi-taraxasterol. See EC 4.2.1.128 (lupan-3beta,20-diol synthase).
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
(18E)-22,23-dihydro-20-oxa-oxidosqualene
3beta-hydroxy-22,23,24,25,26,27-hexanor-17beta-dammaran-20-one + ?
-
the 20-oxa substitution has negligible effect on substrate binding and on the activation energies
sole product
-
?
(3S)-2,3-oxidosqualene
lupeol
-
no discrimination of the terminal two methyl groups of substrate, proton abstraction occurs from both methyl groups in equal ratio. This is in contrast to Olea europea and Taraxacum officinale enzymes, which abstract the proton exclusively from (Z)-methyl of substrate
-
-
?
(3S,22S)-2,3:22,23-dioxidosqualene
(2R,4aR,6aS,6bS,10R,12aS,14aR,14bS)-2-(1-hydroxy-1-methylethyl)-4a,6a,6b,9,9,12a-hexamethylicosahydro-2H-phenanthro[1,2-h]chromen-10-ol + (3alpha,5xi,8alpha,9xi,10alpha,13aalpha,14beta,17xi,20R,24R)-20,24-epoxydammarane-3,25-diol + (3alpha,5xi,8alpha,9xi,10alpha,13alpha,14beta,17xi,24R)-20,24-epoxydammarane-3,25-diol
-
-
products 5_4_99.B3_11.8, 5_4_99.B3_11.9a and 5_4_99.B3_11.9b in ratio 3:4:2, almost complete consumption of substrate
-
?
2,3-oxidosqualene
lupeol + germanicol + beta-amyrin + taraxasterol + psi-taraxasterol + 3,20-dihydroxylupane
-
-
-
-
?
3-(omega-oxidogeranlygeranyl)indole
petromindole
-
substrate undergoes protonation, epoxide ring opening, and chair-chair bicyclization to cation. A Markovnikov intermediate is strongly favored, and its cyclization to indole forms the final product
-
-
?
(3S)-2,3-oxidosqualene
lupeol
-
beta-amyrin is a minor product
-
?
2,3-oxidosqualene
lupeol
-
-
enzyme additionally catalyzes the stereospecific addition of water to yield 3beta,20-dihydroxylupane without rotation of the C19-C20 bond
-
?
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
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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). LUP1_ARATH
757
0
87352
Swiss-Prot
other Location (Reliability: 2)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
construction of chimera between Arabidopsis thaliana YUP8H12R.43 multifunctional triterpene synthase and LUP1 lupeol synthase. Mutant with N-terminal half of LUP1 and C-terminal half of YUP8H12R.43 gives a product pattern similar to native LUP1 with increased production of minor compounds. Mutant LUP1 containing amino acids corresponding to residues 184 to 398 from YUP8H12R.43 gives an almost identical product pattern with native LUP1. Mutant YUP8H12R.43 containing amino acids corresponding to residues 184 to 395 from LUP1 shows similar product multiplicity to that observed in YUP8H12R.43
additional information
construction of chimeric proteins using beta-amyrin synthase from Panax ginseng and lupeol synthase from Arabidopsis thaliana. Chimera with N-terminal half of beta-amyrin synthase and C-terminal half of lupeol synthase produces beta-amyrin and lupeol in ratio 3:1. Chimera with only the second quarter of the N-terminus from beta-amyrin synthase, produces beta-amyrin and lupeol in a 4:1 ratio, while another chimera created by mixed PCR produces beta-amyrin and lupeol in a 1:4 ratio
additional information
functional expression in Saccharomyces cerevisiae lacking lanosterol synthase activity results in production of lupeol
additional information
-
functional expression in Saccharomyces cerevisiae lacking lanosterol synthase activity results in production of lupeol
additional information
2,3-oxidosqualene production is implemented and subsequently combined with different cyclization reactions catalyzed by the representative oxidosqualene cyclases CAS1 (cycloartenol synthase), LUP1 (lupeol synthase), THAS1 (thalianol synthase) and MRN1 (marneral synthase), derived from model plant Arabidopsis thaliana, in the two alternative hosts for biosynthesis of cyclic plant triterpenes, the metabolically versatile photosynthetic alpha-proteobacterium Rhodobacter capsulatus strain SB1003 and cyanobacterium Synechocystis sp. PCC 6803, triterpene pathway design, overview. While successful accumulation of 2,3-oxidosqualene can be detected by LC-MS analysis in both hosts, cyclase expression results in differential production profiles. CAS1 catalyzes conversion to only cycloartenol, but expression of LUP1 yields lupeol and a triterpenoid matching an oxidation product of lupeol, lupX, in both hosts. In contrast, THAS1 expression does not lead to cyclic product formation in either host, whereas MRN1-dependent production of marnerol and hydroxymarnerol is observed in Synechocystis but not in Rhodobacter capsulatus. 2,3-Oxidosqualene cyclization in heterologous phototrophic bacteria is basically feasible but efficient conversion depends on both the respective cyclase enzyme and individual host properties
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Saccharomyces cerevisiae
gene LUP1, recombinant expression in Rhodobacter capsulatus strain SB1003. and Synechocystis sp. PCC 6803 using promoters Pnif and PcoaT, coexpression with CAS1, THAS1, and MRN1. Subcloning in Saccharomyces cerevisiae strain GIL77. Isolation of triterpenes, while cycloartenol and lupeol represent typical plant triterpenes with tetracyclic plant sterol and pentacyclic plant triterpene scaffolds, respectively, thalianol and marneral exhibit more unusual tri- and monocyclic structures. Expression of LUP1 yields lupeol and a triterpenoid matching an oxidation product of lupeol, in both hosts. In Rhodobacter capsulatus and Synechocystis, LUP1-mediated formation of oxidized lupeol derivatives appears to be favored
expression in Saccharomyces cerevisiae lacking lanosterol and ergosterol synthase activities
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expression in Saccharomyces cerevisiae lacking lanosterol synthase activity
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kushiro, T.; Shibuya, M.; Ebizuka, Y.
Chimeric triterpene synthase. A possible model for multifunctional triterpene synthase
J. Am. Chem. Soc.
121
1208-1216
1999
Arabidopsis thaliana (Q9C5M3)
-
Xiong, Q.; Zhu, X.; Wilson, W.K.; Ganesan, A.; Matsuda, S.P.
Enzymatic synthesis of an indole diterpene by an oxidosqualene cyclase: mechanistic, biosynthetic, and phylogenetic implications
J. Am. Chem. Soc.
125
9002-9003
2003
Arabidopsis thaliana
Shan, H.; Segura, M.J.; Wilson, W.K.; Lodeiro, S.; Matsuda, S.P.
Enzymatic cyclization of dioxidosqualene to heterocyclic triterpenes
J. Am. Chem. Soc.
127
18008-18009
2005
Arabidopsis thaliana
Xiong, Q.; Rocco, F.; Wilson, W.K.; Xu, R.; Ceruti, M.; Matsuda, S.P.
Structure and reactivity of the dammarenyl cation: configurational transmission in triterpene synthesis
J. Org. Chem.
70
5362-5375
2005
Arabidopsis thaliana
Segura, M.J.; Meyer, M.M.; Matsuda, S.P.
Arabidopsis thaliana LUP1 converts oxidosqualene to multiple triterpene alcohols and a triterpene diol
Org. Lett.
2
2257-2259
2000
Arabidopsis thaliana
Kushiro, T.; Hoshino, M.; Tsutsumi, T.; Kawai, K.i.; Shiro, M.; Shibuya, M.; Ebizuka, Y.
Stereochemical course in water addition during LUP1-catalyzed triterpene cyclization
Org. Lett.
8
5589-5592
2006
Arabidopsis thaliana
Herrera, J.B.; Bartel, B.; Wilson, W.K.; Matsuda, S.P.
Cloning and characterization of the Arabidopsis thaliana lupeol synthase gene
Phytochemistry
49
1905-1911
1998
Arabidopsis thaliana (Q9C5M3), Arabidopsis thaliana
Husselstein-Muller, T.; Schaller, H.; Benveniste, P.
Molecular cloning and expression in yeast of 2,3-oxidosqualene-triterpenoid cyclases from Arabidopsis thaliana
Plant Mol. Biol.
45
75-92
2001
Arabidopsis thaliana (Q9C5M3), Arabidopsis thaliana
Kushiro, T.; Shibuya, M.; Ebizuka, Y.
Cryptic regiospecificity in deprotonation step of triterpene biosynthesis catalyzed by new members of lupeol synthase
Tetrahedron Lett.
40
5553-5556
1999
Arabidopsis thaliana, Olea europaea, Taraxacum officinale
-
Kushiro, T.; Shibuya, M.; Masuda, K.; Ebizuka, Y.
A novel multifunctional triterpene synthase from Arabidopsis thaliana
Tetrahedron Lett.
41
7705-7710
2000
Arabidopsis thaliana (Q9C5M3)
-
Loeschcke, A.; Dienst, D.; Wewer, V.; Hage-Huelsmann, J.; Dietsch, M.; Kranz-Finger, S.; Hueren, V.; Metzger, S.; Urlacher, V.B.; Gigolashvili, T.; Kopriva, S.; Axmann, I.M.; Drepper, T.; Jaeger, K.E.
The photosynthetic bacteria Rhodobacter capsulatus and Synechocystis sp. PCC 6803 as new hosts for cyclic plant triterpene biosynthesis
PLoS ONE
12
e0189816
2017
Arabidopsis thaliana (Q9C5M3)
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