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Information on EC 5.5.1.32 - 12-epi-hapalindole U synthase
for references in articles please use BRENDA:EC5.5.1.32
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EC Tree 5 Isomerases
5.5 Intramolecular lyases
5.5.1 Intramolecular lyases (only sub-subclass identified to date)
5.5.1.32 12-epi-hapalindole U synthase
IUBMB Comments
The enzyme, characterized from the cyanobacterium Fischerella ambigua UTEX 1903, forms the core structure of the 12-epi-hapalindole family of alkaloids.
The enzyme appears in viruses and cellular organisms
- 5.5.1.32
-
hapalindole-type
-
cyclization
- prenyltransferase
- ambigua
-
cyanobacterial
-
isonitrile
-
polycyclic
-
indolenine
- fischerella
-
geranylated
-
cyclases
showSynonyms
famc1, ambu4, hpic1, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AmbU1
ambU4
famC1
FamC4
HpiC1
Stig cyclase
famC1
-
-
-
-
HpiC1
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole = 12-epi-hapalindole U
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
MetaCyc
12-epi-hapalindole biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole cyclase (12-epi-hapalindole U-forming)
The enzyme, characterized from the cyanobacterium Fischerella ambigua UTEX 1903, forms the core structure of the 12-epi-hapalindole family of alkaloids.
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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
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole
12-epi-hapalindole U
Substrates: -
Products: -
Products: -
?
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole
12-epi-hapalindole U
Substrates: -
Products: -
Products: -
?
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole
12-epi-hapalindole U
Fischerella ambigua UTEX 19030
Substrates: -
Products: -
Products: -
?
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole
12-epi-hapalindole U
-
Substrates: -
Products: -
Products: -
?
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole
12-epi-hapalindole U
-
Substrates: -
Products: -
Products: -
?
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole
12-epi-hapalindole U
Substrates: -
Products: -
Products: -
?
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole
12-epi-hapalindole U
-
Substrates: -
Products: -
Products: -
?
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole
12-epi-hapalindole U
Fischerella sp. IL-199-3-1
-
Substrates: -
Products: -
Products: -
?
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole
12-epi-hapalindole U
-
Substrates: -
Products: -
Products: -
?
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole
hapalindole U
V5TDH6; A0A076N4W8
Substrates: -
Products: -
Products: -
?
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole
hapalindole U
V5TDH6; A0A076N4W8
Substrates: -
Products: -
Products: -
?
5-fluoro-cis-indole isonitrile geranyl diphosphate
5-fluoro-12-epi-hapalindole U
-
Substrates: -
Products: -
Products: -
?
5-fluoro-cis-indole isonitrile geranyl diphosphate
5-fluoro-12-epi-hapalindole U
-
Substrates: -
Products: -
Products: -
?
6-fluoro-cis-indole isonitrile geranyl diphosphate
6-fluoro-12-epi-hapalindole U
-
Substrates: -
Products: -
Products: -
?
6-fluoro-cis-indole isonitrile geranyl diphosphate
6-fluoro-12-epi-hapalindole U
-
Substrates: -
Products: -
Products: -
?
cis-indole isonitrile geranyl diphosphate
(10S,11R,12R,15S)-hapalindole U
-
Substrates: -
Products: -
Products: -
?
cis-indole isonitrile geranyl diphosphate
(10S,11R,12R,15S)-hapalindole U
-
Substrates: -
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
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole
12-epi-hapalindole U
Substrates: -
Products: -
Products: -
?
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole
12-epi-hapalindole U
Substrates: -
Products: -
Products: -
?
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole
12-epi-hapalindole U
-
Substrates: -
Products: -
Products: -
?
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole
12-epi-hapalindole U
-
Substrates: -
Products: -
Products: -
?
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole
12-epi-hapalindole U
-
Substrates: -
Products: -
Products: -
?
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole
12-epi-hapalindole U
Fischerella sp. IL-199-3-1
-
Substrates: -
Products: -
Products: -
?
3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole
12-epi-hapalindole U
-
Substrates: -
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
V5TDH6 i.e. subunit FamC4/AmbU1, A0A076N4W8 i.e. subunit FamC1/AmbU4
V5TDH6; A0A076N4W8
UniProt
brenda
V5TDH6 i.e. subunit FamC4/AmbU1, A0A076N4W8 i.e. subunit FamC1/AmbU4
V5TDH6; A0A076N4W8
UniProt
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
physiological function
enzyme is involved in ring formation and stereochemical control in the biosynthesis of hapalindoles. FamC1 catalyzes formation of 12-epi-hapalindole U
physiological function
aromatic prenyltransferase FamD2 and FamC1 act in concert to form the tetracyclic core ring system of the hapalindoles from cis-indole isonitrile and geranyl diphosphate through a presumed biosynthetic Cope rearrangement and subsequent 6-exo-trig cyclization/electrophilic aromatic substitution reaction
physiological function
-
enzyme is involved in ring formation and stereochemical control in the biosynthesis of hapalindoles. FamC1 catalyzes formation of 12-epi-hapalindole U
-
physiological function
Fischerella ambigua UTEX 19030
-
aromatic prenyltransferase FamD2 and FamC1 act in concert to form the tetracyclic core ring system of the hapalindoles from cis-indole isonitrile and geranyl diphosphate through a presumed biosynthetic Cope rearrangement and subsequent 6-exo-trig cyclization/electrophilic aromatic substitution reaction
-
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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). A0A076N4W8_FISAU
Fischerella ambigua (strain UTEX 1903)
227
0
24735
TrEMBL
-
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
wild-type and mutants W73M/K132M, Y101F, Y101S, F138S, and Y101F/F138S. enzyme is a dimer with two calcium ions per monomer and with the active sites located at the distal ends of the protein dimer
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D214A
mutation of active site residue, complete loss of activity
D214E
mutation of active site residue, complete loss of activity
D214N
mutation of active site residue, complete loss of activity
F138S
substitution to the corresponding serine residue from FimC5, mutant produces a mixture of wild-type major product, hapalindole, and the FimC5 major product, fischerindole
W73M/K132M
introduction of methionine resiudes for crystallization
Y101F/F138S
substitution to the corresponding residues from FimC5, mutant produces a mixture of wild-type major product, hapalindole, and the FimC5 major product, fischerindole
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-NTA agarose column chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
expression in Escherichia coli
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Zhu, Q.; Liu, X.
Discovery of a calcium-dependent enzymatic cascade for the selective assembly of hapalindole-type alkaloids on the biosynthetic origin of hapalindole U
Angew. Chem. Int. Ed. Engl.
56
9062-9066
2017
Fischerella ambigua (V5TDH6 and A0A076N4W8), Fischerella ambigua UTEX 1903 (V5TDH6 and A0A076N4W8)
brenda
Li, S.; Lowell, A.N.; Yu, F.; Raveh, A.; Newmister, S.A.; Bair, N.; Schaub, J.M.; Williams, R.M.; Sherman, D.H.
Hapalindole/ambiguine biogenesis is mediated by a cope rearrangement, C-C bond-forming cascade
J. Am. Chem. Soc.
137
15366-15369
2015
Fischerella ambigua (A0A076N4W8), Fischerella ambigua UTEX 19030 (A0A076N4W8)
brenda
Li, S.; Lowell, A.; Newmister, S.; Yu, F.; Williams, R.; Sherman, D.
Decoding cyclase-dependent assembly of hapalindole and fischerindole alkaloids
Nat. Chem. Biol.
13
467-469
2017
Fischerella ambigua (A0A076N4W8), Fischerella sp. SAG 46.79, Fischerella sp. IL-199-3-1, Fischerella sp. ATCC 43239, Fischerella muscicola, Fischerella ambigua UTEX 1903 (A0A076N4W8), Fischerella muscicola UTEX 1829
brenda
Newmister, S.A.; Li, S.; Garcia-Borras, M.; Sanders, J.N.; Yang, S.; Lowell, A.N.; Yu, F.; Smith, J.L.; Williams, R.M.; Houk, K.N.; Sherman, D.H.
Structural basis of the Cope rearrangement and cyclization in hapalindole biogenesis
Nat. Chem. Biol.
14
345-351
2018
Fischerella sp. ATCC 43239 (A0A076NBW8)
brenda
Khatri, Y.; Hohlman, R.M.; Mendoza, J.; Li, S.; Lowell, A.N.; Asahara, H.; Sherman, D.H.
Multicomponent microscale biosynthesis of unnatural cyanobacterial indole alkaloids
ACS Synth. Biol.
9
1349-1360
2020
Fischerella ambigua, Fischerella ambigua UTEX 1903
brenda
EXTERNAL LINKS (specific for EC-Number 5.5.1.32)
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