ASQG_EMENI
ID ASQG_EMENI Reviewed; 566 AA.
AC Q5AR50; C8VJP9;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=FAD-dependent monooxygenase asqG {ECO:0000303|PubMed:25251934};
DE EC=1.-.-.- {ECO:0000269|PubMed:28114276};
DE AltName: Full=4'-methoxyviridicatin/aspoquinolone biosynthesis cluster protein asqG {ECO:0000305};
DE AltName: Full=Aspoquinolone biosynthesis protein G {ECO:0000303|PubMed:25251934};
DE Flags: Precursor;
GN Name=asqG {ECO:0000303|PubMed:25251934}; ORFNames=AN9230;
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, CATALYTIC ACTIVITY, AND PATHWAY.
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]
RP FUNCTION.
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: FAD-dependent monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of the aspoquinolone mycotoxins
CC (PubMed:25251934, PubMed:28114276). The first stage is catalyzed by the
CC nonribosomal pepdide synthetase asqK that condenses anthranilic acid
CC and O-methyl-L-tyrosine to produce 4'-methoxycyclopeptin
CC (PubMed:25251934, PubMed:28114276). AsqK is also able to use
CC anthranilic acid and L-phenylalanine as substrates to produce
CC 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:28114276, ECO:0000269|PubMed:30026518,
CC ECO:0000305|PubMed:30026518}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:28114276}.
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:28114276}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:28114276}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; BN001306; CBF82272.1; -; Genomic_DNA.
DR EMBL; AACD01000170; EAA61521.1; -; Genomic_DNA.
DR RefSeq; XP_682499.1; XM_677407.1.
DR AlphaFoldDB; Q5AR50; -.
DR SMR; Q5AR50; -.
DR STRING; 162425.CADANIAP00009360; -.
DR EnsemblFungi; CBF82272; CBF82272; ANIA_09230.
DR EnsemblFungi; EAA61521; EAA61521; AN9230.2.
DR GeneID; 2868012; -.
DR KEGG; ani:AN9230.2; -.
DR eggNOG; KOG2614; Eukaryota.
DR HOGENOM; CLU_009665_12_2_1; -.
DR InParanoid; Q5AR50; -.
DR OMA; RELEWAG; -.
DR OrthoDB; 462247at2759; -.
DR Proteomes; UP000000560; Chromosome VI.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Membrane; Monooxygenase; Oxidoreductase;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..566
FT /note="FAD-dependent monooxygenase asqG"
FT /id="PRO_0000437618"
FT TRANSMEM 448..468
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 482..502
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 34..35
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 313
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 323..327
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
SQ SEQUENCE 566 AA; 61875 MW; D2B220D263CC2D82 CRC64;
MAAFTVIIIG GSISGLTLAN VLEKYGIKYI LLEKRPSIGP QLGATVVVHP SGLHLLSQLG
LRERVEELAT PVELQKAIGP DGTFVLNIAA TNQCDRTIAD ALSTGYMPMF IARQDLIKVL
YDNLQDKFRV HASLGLRELE WAGDKVKVTT TDGTSVVGDI VVGADGANSR TRAEIWKIAD
VEDPSYGSQQ LAKSIACTYR CVFGMVDDGD SSLARTAYLA FQYNRAYTYL PTDSGRAYFL
AFFKNPAKTV NDAIPRYSDQ DEDADVAAHA NDIIVPGLTF GDLYKRRTRC TLVPLQEYLL
DKCFYKRVVL IGDAVHKLNP ITGRGANLAI EGAALLGDLI KHALEKSLQP TDEMLQTAFF
TYQQCTKSRA PSQIDDAHRV QSLAALENPL LKFMSLKLLK RATADKLALG VAVDFSTGHS
MRYLPQLPQR GMVPLNKDVV ANPEHRPASS TVLWIILMLG MASLGAVWQK HQRAEEDQPI
HGYTLLTLST FYNLMILFAS AVHGSLGRRA VNLSFSDDSG MVPFYAVGHA PDKYRPTTPS
RRVGLLVPGP SYLGSGGHFN GLLEVA
