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 22-FEB-2023, entry version 95. 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 -!- CATALYTIC ACTIVITY: CC Reaction=[(1'E)-3'-hydroxy-3',7'-dimethylocta-1',6'-dien-1'-yl]- CC quinolinone B + H(+) + NADPH + O2 = [(1'E)-5'-(3',3'-dimethyloxiran- CC 2'-yl)-3'-hydroxy-3'-methylpent-1'-en-1'-yl]-quinolinone B + H2O + CC NADP(+); Xref=Rhea:RHEA:74011, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, CC ChEBI:CHEBI:193078, ChEBI:CHEBI:193079; CC Evidence={ECO:0000269|PubMed:28114276}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:74012; CC Evidence={ECO:0000269|PubMed:28114276}; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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; 2332834at2759; -. DR Proteomes; UP000000560; Chromosome VI. DR Proteomes; UP000005890; Unassembled WGS sequence. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell. 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; FAD/NAD(P)-binding domain; 1. DR InterPro; IPR002938; FAD-bd. DR InterPro; IPR036188; FAD/NAD-bd_sf. DR PANTHER; PTHR47356; FAD-DEPENDENT MONOOXYGENASE ASQG-RELATED; 1. DR PANTHER; PTHR47356:SF2; FAD-DEPENDENT MONOOXYGENASE ASQG-RELATED; 1. DR Pfam; PF01494; FAD_binding_3; 1. DR PRINTS; PR00420; RNGMNOXGNASE. DR SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 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 //