KEGG   ENZYME: 1.14.11.81
Entry
EC 1.14.11.81               Enzyme                                 
Name
(-)-cyclopenine synthase;
asqJ (gene name)
Class
Oxidoreductases;
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With 2-oxoglutarate as one donor, and incorporation of one atom of oxygen into each donor
Sysname
cyclopeptine,2-oxoglutarate:oxygen oxidoreductase ((-)-cyclopenine-forming)
Reaction(IUBMB)
(1) cyclopeptine + 2-oxoglutarate + O2 = dehydrocyclopeptine + succinate + CO2 + H2O [RN:R13110];
(2) dehydrocyclopeptine + 2-oxoglutarate + O2 = (-)-cyclopenine + succinate + CO2 [RN:R13111]
Reaction(KEGG)
R13110 R13111
Substrate
cyclopeptine [CPD:C20579];
2-oxoglutarate [CPD:C00026];
O2 [CPD:C00007];
dehydrocyclopeptine [CPD:C22622]
Product
dehydrocyclopeptine [CPD:C22622];
succinate [CPD:C00042];
CO2 [CPD:C00011];
H2O [CPD:C00001];
(-)-cyclopenine [CPD:C22623]
Comment
This fungal enzyme is involved in the biosynthesis of quinolone compounds. it catalyses two oxidation reactions: the first reaction results in a desaturation; the second reaction is a monooxygenation of the double bond, forming an epoxide. The enzyme is also active with 4'-methoxycyclopeptine.
History
EC 1.14.11.81 created 2022
Orthology
K26347  (-)-cyclopenine synthase
Genes
ANIANIA_09227
Reference
1  [PMID:11947032]
  Authors
Nover L, Luckner M.
  Title
Mixed functional oxygenations during the biosynthesis of cyclopenin and cyclopenol, benzodiazepine alkaloids of penicillium cyclopium westling. Incorporation of molecular oxygen and NIH-shift.
  Journal
FEBS Lett 3:292-296 (1969)
DOI:10.1016/0014-5793(69)80161-4
Reference
2  [PMID:25251934]
  Authors
Ishikawa N, Tanaka H, Koyama F, Noguchi H, Wang CC, Hotta K, Watanabe K
  Title
Non-heme dioxygenase catalyzes atypical oxidations of 6,7-bicyclic systems to form the 6,6-quinolone core of viridicatin-type fungal alkaloids.
  Journal
Angew Chem Int Ed Engl 53:12880-4 (2014)
DOI:10.1002/anie.201407920
  Sequence
Reference
3  [PMID:26553478]
  Authors
Brauer A, Beck P, Hintermann L, Groll M.
  Title
Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis.
  Journal
Angew Chem Int Ed Engl 55:422-6 (2016)
DOI:10.1002/anie.201507835
  Sequence
Reference
4  [PMID:27442345]
  Authors
Chang WC, Li J, Lee JL, Cronican AA, Guo Y.
  Title
Mechanistic Investigation of a Non-Heme Iron Enzyme Catalyzed Epoxidation in (-)-4'-Methoxycyclopenin Biosynthesis.
  Journal
J Am Chem Soc 138:10390-3 (2016)
DOI:10.1021/jacs.6b05400
  Sequence
Reference
5  [PMID:28726913]
  Authors
Song X, Lu J, Lai W.
  Title
Mechanistic insights into dioxygen activation, oxygen atom exchange and substrate epoxidation by AsqJ dioxygenase from quantum mechanical/molecular mechanical calculations.
  Journal
Phys Chem Chem Phys 19:20188-20197 (2017)
DOI:10.1039/c7cp02687k
  Sequence
Reference
6  [PMID:29314482]
  Authors
Liao HJ, Li J, Huang JL, Davidson M, Kurnikov I, Lin TS, Lee JL, Kurnikova M, Guo Y, Chan NL, Chang WC.
  Title
Insights into the Desaturation of Cyclopeptin and its C3 Epimer Catalyzed by a non-Heme Iron Enzyme: Structural Characterization and Mechanism Elucidation.
  Journal
Angew Chem Int Ed Engl 57:1831-1835 (2018)
DOI:10.1002/anie.201710567
  Sequence
Reference
7  [PMID:29563492]
  Authors
Mader SL, Brauer A, Groll M, Kaila VRI.
  Title
Catalytic mechanism and molecular engineering of quinolone biosynthesis in dioxygenase AsqJ.
  Journal
Nat Commun 9:1168 (2018)
DOI:10.1038/s41467-018-03442-2
  Sequence
Reference
8  [PMID:29876666]
  Authors
Wojdyla Z, Borowski T.
  Title
On how the binding cavity of AsqJ dioxygenase controls the desaturation reaction regioselectivity: a QM/MM study.
  Journal
J Biol Inorg Chem 23:795-808 (2018)
DOI:10.1007/s00775-018-1575-3
  Sequence
Reference
9  [PMID:32131594]
  Authors
Li J, Liao HJ, Tang Y, Huang JL, Cha L, Lin TS, Lee JL, Kurnikov IV, Kurnikova MG, Chang WC, Chan NL, Guo Y.
  Title
Epoxidation Catalyzed by the Nonheme Iron(II)- and 2-Oxoglutarate-Dependent Oxygenase, AsqJ: Mechanistic Elucidation of Oxygen Atom Transfer by a Ferryl Intermediate.
  Journal
J Am Chem Soc 142:6268-6284 (2020)
DOI:10.1021/jacs.0c00484
  Sequence
Reference
10 [PMID:35721870]
  Authors
Tang H, Tang Y, Kurnikov IV, Liao HJ, Chan NL, Kurnikova MG, Guo Y, Chang WC.
  Title
Harnessing the Substrate Promiscuity of Dioxygenase AsqJ and Developing Efficient Chemoenzymatic Synthesis for Quinolones.
  Journal
ACS Catal 11:7186-7192 (2021)
DOI:10.1021/acscatal.1c01150
  Sequence
Other DBs
ExplorEnz - The Enzyme Database: 1.14.11.81
IUBMB Enzyme Nomenclature: 1.14.11.81
ExPASy - ENZYME nomenclature database: 1.14.11.81
BRENDA, the Enzyme Database: 1.14.11.81

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