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 13-SEP-2023, entry version 98. 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, 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). CC -!- FUNCTION: FAD-dependent monooxygenase; part of the gene cluster that CC mediates the biosynthesis of the aspoquinolone mycotoxins CC (PubMed:25251934, PubMed:28114276). Within the pathway, the FAD- CC dependent monooxygenase asqG catalyzes the epoxidation of the terminal CC C7'-C8' olefin to produce the intermediate [(1'E)-5'-(3',3'- CC dimethyloxiran-2'-yl)-3'-hydroxy-3'-methylpent-1'-en-1'-yl]-quinolinone CC B (PubMed:28114276). The first step of the pathway is catalyzed by the CC nonribosomal pepdide synthetase asqK that condenses anthranilic acid CC and O-methyl-L-tyrosine to produce 4'-methoxycyclopeptin. 4'- CC methoxycyclopeptin is then converted to 4'-methoxydehydrocyclopeptin by CC the ketoglutarate-dependent dioxygenase asqJ. AsqJ also converts its CC first product 4'-methoxydehydrocyclopeptin to 4'-methoxycyclopenin. The CC following conversion of 4'-methoxycyclopenin into 4'-methoxyviridicatin CC is catalyzed by the cyclopenase asqI. 4'-methoxyviridicatin is the CC precursor of quinolone natural products, and is further converted to CC quinolinone B. 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. The delta(3') double bond then serves as the CC 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. The FAD-dependent monooxygenase asqG performs CC epoxidation of the terminal C7'-C8' olefin. Finally, after CC dehydratation of the epoxide at C3 by asqC, the quinolone epoxide CC rearrangement protein asqO catalyzes an enzymatic 3-exo-tet cyclization CC to yield the cyclopropyl-THF ring system in aspoquinolone (Probable). CC {ECO:0000269|PubMed:25251934, ECO:0000269|PubMed:28114276, CC ECO:0000305}. 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 BioCyc; MetaCyc:MONOMER-124180; -. 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 33 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:B8M9J8" FT BINDING 47 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:B8M9J8" FT BINDING 113 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:B8M9J8" FT BINDING 313 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:B8M9J8" FT BINDING 326 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:B8M9J8" 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 //