EC |
1.14.11.81 |
Accepted name: |
(–)-cyclopenine synthase |
Reaction: |
(1) cyclopeptine + 2-oxoglutarate + O2 = dehydrocyclopeptine + succinate + CO2 + H2O (2) dehydrocyclopeptine + 2-oxoglutarate + O2 = (–)-cyclopenine + succinate + CO2 |
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For diagram of cyclopeptine, cyclopenine and viridicatin biosynthesis, click here |
Glossary: |
cyclopeptine = (3S)-3-benzyl-4-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione
(–)-cyclopenine = (3S,3′R)-4-methyl-3′-phenyl-1H-spiro[1,4-benzodiazepine-3,2′-oxirane]-2,5-dione |
Other name(s): |
asqJ (gene name) |
Systematic name: |
cyclopeptine,2-oxoglutarate:oxygen oxidoreductase ((–)-cyclopenine-forming) |
Comments: |
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. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Nover, L. and Luckner, M. Mixed functional oxygenations during the biosynthesis of cyclopenin and cyclopenol, benzodiazepine alkaloids of Penicillium cyclopium westling. Incorporation of molecular oxygen and NIH-shift. FEBS Lett. 3 (1969) 292–296. [DOI] [PMID: 11947032] |
2. |
Ishikawa, N., Tanaka, H., Koyama, F., Noguchi, H., Wang, C.C., Hotta, K. and Watanabe, K. Non-heme dioxygenase catalyzes atypical oxidations of 6,7-bicyclic systems to form the 6,6-quinolone core of viridicatin-type fungal alkaloids. Angew. Chem. Int. Ed. Engl. 53 (2014) 12880–12884. [DOI] [PMID: 25251934] |
3. |
Brauer, A., Beck, P., Hintermann, L. and Groll, M. Structure of the dioxygenase AsqJ: Mechanistic insights into a one-pot multistep quinolone antibiotic biosynthesis. Angew. Chem. Int. Ed. Engl. 55 (2016) 422–426. [DOI] [PMID: 26553478] |
4. |
Chang, W.C., Li, J., Lee, J.L., Cronican, A.A. and Guo, Y. Mechanistic investigation of a non-heme iron enzyme catalyzed epoxidation in (–)-4′-methoxycyclopenin biosynthesis. J. Am. Chem. Soc. 138 (2016) 10390–10393. [DOI] [PMID: 27442345] |
5. |
Song, X., Lu, J. and Lai, W. Mechanistic insights into dioxygen activation, oxygen atom exchange and substrate epoxidation by AsqJ dioxygenase from quantum mechanical/molecular mechanical calculations. Phys Chem Chem Phys 19 (2017) 20188–20197. [DOI] [PMID: 28726913] |
6. |
Liao, H.J., Li, J., Huang, J.L., Davidson, M., Kurnikov, I., Lin, T.S., Lee, J.L., Kurnikova, M., Guo, Y., Chan, N.L. and Chang, W.C. Insights into the desaturation of cyclopeptin and its C3 epimer catalyzed by a non-heme iron enzyme: structural characterization and mechanism elucidation. Angew. Chem. Int. Ed. Engl. 57 (2018) 1831–1835. [DOI] [PMID: 29314482] |
7. |
Mader, S.L., Brauer, A., Groll, M. and Kaila, V.RI. Catalytic mechanism and molecular engineering of quinolone biosynthesis in dioxygenase AsqJ. Nat. Commun. 9:1168 (2018). [DOI] [PMID: 29563492] |
8. |
Wojdyla, Z. and Borowski, T. On how the binding cavity of AsqJ dioxygenase controls the desaturation reaction regioselectivity: a QM/MM study. J. Biol. Inorg. Chem. 23 (2018) 795–808. [DOI] [PMID: 29876666] |
9. |
Li, J., Liao, H.J., Tang, Y., Huang, J.L., Cha, L., Lin, T.S., Lee, J.L., Kurnikov, I.V., Kurnikova, M.G., Chang, W.C., Chan, N.L. and Guo, Y. Epoxidation catalyzed by the nonheme iron(II)- and 2-oxoglutarate-dependent oxygenase, AsqJ: mechanistic elucidation of oxygen atom transfer by a ferryl intermediate. J. Am. Chem. Soc. 142 (2020) 6268–6284. [DOI] [PMID: 32131594] |
10. |
Tang, H., Tang, Y., Kurnikov, I.V., Liao, H.J., Chan, N.L., Kurnikova, M.G., Guo, Y. and Chang, W.C. Harnessing the substrate promiscuity of dioxygenase AsqJ and developing efficient chemoenzymatic synthesis for quinolones. ACS Catal. 11 (2021) 7186–7192. [DOI] [PMID: 35721870] |
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[EC 1.14.11.81 created 2022] |
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EC
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2.7.7.54
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Deleted entry: | phenylalanine adenylyltransferase. The activity is part of EC 6.3.2.40, cyclopeptine synthase. |
[EC 2.7.7.54 created 1989, deleted 2013] |
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EC
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2.7.7.55
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Deleted entry: | anthranilate adenylyltransferase. The activity is part of EC 6.3.2.40, cyclopeptine synthase. |
[EC 2.7.7.55 created 1989, deleted 2013] |
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EC |
4.1.99.27 |
Accepted name: |
cyclopenase |
Reaction: |
(–)-cyclopenine = viridicatin + methyl isocyanate |
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For diagram of cyclopeptine, cyclopenine and viridicatin biosynthesis, click here |
Glossary: |
(–)-cyclopenine = (3S,3′R)-4-methyl-3′-phenyl-1H-spiro[1,4-benzodiazepine-3,2′-oxirane]-2,5-dione
viridicatin = 3-hydroxy-4-phenyl-1H-quinolin-2-one |
Other name(s): |
asqI (gene name) |
Systematic name: |
(–)-cyclopenine methyl-isocyanate lyase (viridicatin-forming) |
Comments: |
This fungal enzyme catalyses a key reaction in the biosynthesis of quinolone compounds, converting the benzodiazepine structure into a quinolone structure. The enzyme is also active with (–)-4′-methoxycyclopenine. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Kishimoto, S., Hara, K., Hashimoto, H., Hirayama, Y., Champagne, P.A., Houk, K.N., Tang, Y. and Watanabe, K. Enzymatic one-step ring contraction for quinolone biosynthesis. Nat. Commun. 9:2826 (2018). [DOI] [PMID: 30026518] |
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[EC 4.1.99.27 created 2022] |
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EC |
6.3.2.40 |
Accepted name: |
cyclopeptine synthase |
Reaction: |
2 ATP + S-adenosyl-L-methionine + anthranilate + L-phenylalanine = cyclopeptine + 2 AMP + 2 diphosphate + S-adenosyl-L-homocysteine |
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For diagram of cyclopeptine, cyclopenine and viridicatin biosynthesis, click here |
Glossary: |
cyclopeptine = (3S)-3-benzyl-4-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione
4′-methoxycyclopeptine = (3S)-3-(4-methoxybenzyl)-4-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione |
Systematic name: |
S-adenosyl-L-methionine:anthranilate:L-phenylalanine ligase (cyclopeptine-forming) |
Comments: |
Cyclopeptine synthase is the key enzyme of benzodiazepine alkaloid biosynthesis in several fungi species. The enzyme is a non-ribosomal peptide synthase. It is also active with O-methyl-L-tyrosine forming 4′-methoxycyclopeptine. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Lerbs, W. and Luckner, M. Cyclopeptine synthetase activity in surface cultures of Penicillium cyclopium. J. Basic Microbiol. 25 (1985) 387–391. [DOI] [PMID: 2995633] |
2. |
Gerlach, M, Schwelle, N., Lerbs, W. and Luckner, M. Enzymatic synthesis of cyclopeptine intermediates in Penicillium cyclopium. Phytochemistry 24 (1985) 1935–1939. |
3. |
Ishikawa, N., Tanaka, H., Koyama, F., Noguchi, H., Wang, C.C., Hotta, K. and Watanabe, K. Non-heme dioxygenase catalyzes atypical oxidations of 6,7-bicyclic systems to form the 6,6-quinolone core of viridicatin-type fungal alkaloids. Angew. Chem. Int. Ed. Engl. 53 (2014) 12880–12884. [DOI] [PMID: 25251934] |
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[EC 6.3.2.40 created 2013] |
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