ASQI_EMENI
ID ASQI_EMENI Reviewed; 732 AA.
AC C8VJQ3; Q5AR52;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 1.
DT 03-AUG-2022, entry version 50.
DE RecName: Full=Cyclopenase asqI {ECO:0000303|PubMed:25251934};
DE EC=1.-.-.- {ECO:0000269|PubMed:30026518};
DE AltName: Full=4'-methoxyviridicatin/aspoquinolone biosynthesis cluster protein asqI {ECO:0000305};
DE AltName: Full=Aspoquinolone biosynthesis protein I {ECO:0000303|PubMed:25251934};
GN Name=asqI {ECO:0000303|PubMed:25251934}; ORFNames=AN9228, ANIA_11193;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
RN [3]
RP FUNCTION.
RX PubMed=25251934; DOI=10.1002/anie.201407920;
RA Ishikawa N., Tanaka H., Koyama F., Noguchi H., Wang C.C., Hotta K.,
RA Watanabe K.;
RT "Non-heme dioxygenase catalyzes atypical oxidations of 6,7-bicyclic systems
RT to form the 6,6-quinolone core of viridicatin-type fungal alkaloids.";
RL Angew. Chem. Int. Ed. 53:12880-12884(2014).
RN [4]
RP FUNCTION.
RX PubMed=26553478; DOI=10.1002/anie.201507835;
RA Brauer A., Beck P., Hintermann L., Groll M.;
RT "Structure of the dioxygenase AsqJ: mechanistic insights into a one-pot
RT multistep quinolone antibiotic biosynthesis.";
RL Angew. Chem. Int. Ed. 55:422-426(2016).
RN [5]
RP FUNCTION.
RX PubMed=28114276; DOI=10.1038/nchembio.2283;
RA Zou Y., Garcia-Borras M., Tang M.C., Hirayama Y., Li D.H., Li L.,
RA Watanabe K., Houk K.N., Tang Y.;
RT "Enzyme-catalyzed cationic epoxide rearrangements in quinolone alkaloid
RT biosynthesis.";
RL Nat. Chem. Biol. 13:325-332(2017).
RN [6] {ECO:0007744|PDB:5YY2, ECO:0007744|PDB:5YY3}
RP X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) OF 1-731 IN COMPLEX WITH ZINC,
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR,
RP PATHWAY, AND MUTAGENESIS OF HIS-168; HIS-172; ARG-176; HIS-200; ASP-314;
RP HIS-338 AND ASN-339.
RX PubMed=30026518; DOI=10.1038/s41467-018-05221-5;
RA Kishimoto S., Hara K., Hashimoto H., Hirayama Y., Champagne P.A.,
RA Houk K.N., Tang Y., Watanabe K.;
RT "Enzymatic one-step ring contraction for quinolone biosynthesis.";
RL Nat. Commun. 9:2826-2826(2018).
CC -!- FUNCTION: Cyclopenase; part of the gene cluster that mediates the
CC biosynthesis of the aspoquinolone mycotoxins (PubMed:25251934,
CC PubMed:30026518). The first stage is catalyzed by the nonribosomal
CC pepdide synthetase asqK that condenses anthranilic acid and O-methyl-L-
CC tyrosine to produce 4'-methoxycyclopeptin (PubMed:25251934). AsqK is
CC also able to use anthranilic acid and L-phenylalanine as substrates to
CC produce cyclopeptin, but at a tenfold lower rate (PubMed:25251934). 4'-
CC methoxycyclopeptin is then converted to 4'-methoxydehydrocyclopeptin by
CC the ketoglutarate-dependent dioxygenase asqJ through dehydrogenation to
CC form a double bond between C-alpha and C-beta of the O-methyltyrosine
CC side chain (PubMed:25251934, PubMed:26553478). AsqJ also converts its
CC first product 4'-methoxydehydrocyclopeptin to 4'-methoxycyclopenin
CC (PubMed:25251934). AsqJ is a very unique dioxygenase which is capable
CC of catalyzing radical-mediated dehydrogenation and epoxidation
CC reactions sequentially on a 6,7-benzo-diazepinedione substrate in the
CC 4'-methoxyviridicatin biosynthetic pathway (PubMed:25251934). AsqJ is
CC also capable of converting cyclopeptin into dehydrocyclopeptin
CC (PubMed:25251934). The following conversion of 4'-methoxycyclopenin
CC into 4'-methoxyviridicatin is catalyzed by the cyclopenase asqI
CC (PubMed:30026518). Cyclopenin can also be converted into viridicatin by
CC asqI (PubMed:30026518). 4'-methoxyviridicatin is the precursor of
CC quinolone natural products, and is further converted to quinolinone B
CC (Probable). The prenyltransferase asqH1 then catalyzes the canonical
CC Friedel-Crafts alkylation of quinolinone B with dimethylallyl cation to
CC yield dimethylallyl quinolone, which is subjected to FAD-dependent
CC dehydrogenation by the FAD-linked oxidoreductase asqF to yield
CC conjugated aryl diene (By similarity). The delta(3') double bond then
CC serves as the site of the second alkylation with DMAPP catalyzed by the
CC prenyltransferase asqH2 to yield a carbenium ion intermediate, which
CC can be attacked by H(2)O to yield a styrenyl quinolone containing a
CC C3'-hydroxyprenyl chain (By similarity). The FAD-dependent
CC monooxygenase asqG performs epoxidation of the terminal C7'-C8' olefin
CC (PubMed:30026518). Finally, after dehydratation of the epoxide at C3 by
CC asqC, the quinolone epoxide rearrangement protein asqO catalyzes an
CC enzymatic 3-exo-tet cyclization to yield the cyclopropyl-THF ring
CC system in aspoquinolone (PubMed:30026518).
CC {ECO:0000250|UniProtKB:A0A1B2CTB2, ECO:0000250|UniProtKB:A0A1B2CTB7,
CC ECO:0000269|PubMed:25251934, ECO:0000269|PubMed:26553478,
CC ECO:0000269|PubMed:30026518, ECO:0000305|PubMed:30026518}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:30026518};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:30026518};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.068 mM for (-)-Cyclopeptin {ECO:0000269|PubMed:30026518};
CC KM=2.86 mM for 4'-methoxycyclopenin {ECO:0000269|PubMed:30026518};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:30026518}.
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:30026518}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:30026518}.
CC -!- SIMILARITY: Belongs to the tyrosinase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAA61519.1; Type=Erroneous gene model prediction; Note=The predicted gene AN9228 has been split into 2 genes: asqI and asqO.; Evidence={ECO:0000269|PubMed:28114276};
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DR EMBL; AACD01000170; EAA61519.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BN001306; CBF82279.1; -; Genomic_DNA.
DR RefSeq; XP_682497.1; XM_677405.1.
DR PDB; 5YY2; X-ray; 2.91 A; A=1-731.
DR PDB; 5YY3; X-ray; 2.31 A; A=1-731.
DR PDBsum; 5YY2; -.
DR PDBsum; 5YY3; -.
DR SMR; C8VJQ3; -.
DR STRING; 227321.C8VJQ3; -.
DR EnsemblFungi; CBF82279; CBF82279; ANIA_11193.
DR GeneID; 2868027; -.
DR VEuPathDB; FungiDB:AN11193; -.
DR HOGENOM; CLU_378560_0_0_1; -.
DR InParanoid; C8VJQ3; -.
DR OMA; QFLTGNM; -.
DR OrthoDB; 254693at2759; -.
DR Proteomes; UP000000560; Chromosome VI.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR Gene3D; 1.10.1280.10; -; 1.
DR Gene3D; 2.60.40.1520; -; 1.
DR InterPro; IPR008922; Di-copper_centre_dom_sf.
DR InterPro; IPR013788; Hemocyanin/hexamerin.
DR InterPro; IPR000896; Hemocyanin/hexamerin_mid_dom.
DR InterPro; IPR005203; Hemocyanin_C.
DR InterPro; IPR037020; Hemocyanin_C_sf.
DR InterPro; IPR014756; Ig_E-set.
DR PANTHER; PTHR11511; PTHR11511; 1.
DR Pfam; PF03723; Hemocyanin_C; 1.
DR Pfam; PF00372; Hemocyanin_M; 1.
DR PRINTS; PR00187; HAEMOCYANIN.
DR SUPFAM; SSF48056; SSF48056; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome; Zinc.
FT CHAIN 1..732
FT /note="Cyclopenase asqI"
FT /id="PRO_0000437623"
FT BINDING 168
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:30026518,
FT ECO:0007744|PDB:5YY2"
FT BINDING 172
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:30026518,
FT ECO:0007744|PDB:5YY2"
FT BINDING 200
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:30026518,
FT ECO:0007744|PDB:5YY2"
FT MUTAGEN 168
FT /note="H->A: Impairs the catalytic activity."
FT /evidence="ECO:0000269|PubMed:30026518"
FT MUTAGEN 172
FT /note="H->A: Impairs the catalytic activity."
FT /evidence="ECO:0000269|PubMed:30026518"
FT MUTAGEN 176
FT /note="R->A: Impairs the catalytic activity."
FT /evidence="ECO:0000269|PubMed:30026518"
FT MUTAGEN 200
FT /note="H->A: Impairs the catalytic activity."
FT /evidence="ECO:0000269|PubMed:30026518"
FT MUTAGEN 314
FT /note="D->L: Impairs the catalytic activity."
FT /evidence="ECO:0000269|PubMed:30026518"
FT MUTAGEN 338
FT /note="H->A: Does not affect the catalytic activity."
FT /evidence="ECO:0000269|PubMed:30026518"
FT MUTAGEN 339
FT /note="N->L: Impairs the catalytic activity."
FT /evidence="ECO:0000269|PubMed:30026518"
SQ SEQUENCE 732 AA; 83554 MW; 2F1CDF926E0154F3 CRC64;
MTCTLRDLNS LLEICCRCPA HNPSTAFAPT TKVRVSSDVR GIFALPVQKD HKPYNGLSPE
HLETMKAVSL MLDAAGPKLE DGISKAKELL EERINPELMR DALGIYLTHS KDAQQRKIFP
PPLKNHPFFS TKTRRPANVA GEICTADTLH GHALLSYWRD DYDLNDSHYY WHMVYRGAGG
DNSKNVGDFD RHGEVFLYVH SQMVARYETE SLCWSLPLVR PWNQYDDFLE NGYAPISSLI
EHYGGYPPFS TWYSIRNPDM PDTLNVTIPR ARLEEWRDNI YAAIRKGQFE TTSKDKPLVL
TRDNCLNFVG GILDAQYPSL NKLLGGCSLD EERYGNLHNY GLGKFAEMAY RNKPGEKSPY
GLTISNFGAP RDPCFWRWYK HLQYYGRLAA TRYPQDITAH RAEVVLSNLV VRLQDRSSPH
YLDGHITTFL GPPAVNFMES KAKLGHEPYE WNVQVKSCRR SPPSKENPQT LTLRLFIAAE
DLMNDYHSWI EMDRATVQLT DESAITKVRL DTDSSVARKM GNYGEPDPRY ASAVFRHGWP
QNLMLPVGKV EGMPFVAFCI ATDDGIPDPA PAPPFHHYHD PRGMGYPFNR AWTQLTEDST
GKASIRTIIS NAELYPFITS TTFKIYRTTK FETKQIIQPT TVTWFNTIRG YFKDADRACM
RSEYGYDLYN YDHVMLHADA ILDATASKRM PLQMGKYTQD NPDPEHPLWT VKMCENFRAW
LLNGCPKGTD PA
