ASQK_EMENI
ID ASQK_EMENI Reviewed; 2559 AA.
AC Q5AR54; C8VJQ5;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Nonribosomal peptide synthetase asqK {ECO:0000303|PubMed:25251934};
DE Short=NRPS asqK {ECO:0000303|PubMed:25251934};
DE EC=6.3.2.- {ECO:0000269|PubMed:25251934};
DE AltName: Full=4'-methoxyviridicatin/aspoquinolone biosynthesis cluster protein asqK {ECO:0000305};
DE AltName: Full=Aspoquinolone biosynthesis protein K {ECO:0000303|PubMed:25251934};
GN Name=asqK {ECO:0000303|PubMed:25251934}; ORFNames=AN9226;
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, AND CATALYTIC ACTIVITY.
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]
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: Nonribosomal peptide synthetase; part of the gene cluster
CC that mediates the biosynthesis of the aspoquinolone mycotoxins
CC (PubMed:25251934). 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 -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:25251934}.
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:25251934}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:25251934}.
CC -!- DOMAIN: NRP synthetases are composed of discrete domains (adenylation
CC (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation
CC (C) domains) which when grouped together are referred to as a single
CC module. Each module is responsible for the recognition (via the A
CC domain) and incorporation of a single amino acid into the growing
CC peptide product. Thus, an NRP synthetase is generally composed of one
CC or more modules and can terminate in a thioesterase domain (TE) that
CC releases the newly synthesized peptide from the enzyme. Occasionally,
CC methyltransferase domains (responsible for amino acid methylation) are
CC present within the NRP synthetase. AsqK has the following
CC architecture:A-T-C-A-M-T-C. {ECO:0000305|PubMed:25251934}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; BN001306; CBF82283.1; -; Genomic_DNA.
DR EMBL; AACD01000170; EAA61517.1; -; Genomic_DNA.
DR RefSeq; XP_682495.1; XM_677403.1.
DR AlphaFoldDB; Q5AR54; -.
DR SMR; Q5AR54; -.
DR STRING; 162425.CADANIAP00009366; -.
DR PRIDE; Q5AR54; -.
DR EnsemblFungi; CBF82283; CBF82283; ANIA_09226.
DR EnsemblFungi; EAA61517; EAA61517; AN9226.2.
DR GeneID; 2868069; -.
DR KEGG; ani:AN9226.2; -.
DR eggNOG; KOG1178; Eukaryota.
DR HOGENOM; CLU_000022_60_1_1; -.
DR InParanoid; Q5AR54; -.
DR OMA; LVCIDYM; -.
DR OrthoDB; 4243at2759; -.
DR Proteomes; UP000000560; Chromosome VI.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IBA:GO_Central.
DR GO; GO:0043041; P:amino acid activation for nonribosomal peptide biosynthetic process; IBA:GO_Central.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IBA:GO_Central.
DR Gene3D; 1.10.1200.10; -; 2.
DR Gene3D; 3.30.300.30; -; 3.
DR Gene3D; 3.30.559.10; -; 3.
DR Gene3D; 3.40.50.12780; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR013216; Methyltransf_11.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF00501; AMP-binding; 2.
DR Pfam; PF00668; Condensation; 2.
DR Pfam; PF08241; Methyltransf_11; 1.
DR Pfam; PF00550; PP-binding; 2.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF53335; SSF53335; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR PROSITE; PS00455; AMP_BINDING; 2.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Isomerase; Ligase; Methyltransferase; Phosphopantetheine; Phosphoprotein;
KW Reference proteome; Repeat; Transferase.
FT CHAIN 1..2559
FT /note="Nonribosomal peptide synthetase asqK"
FT /id="PRO_0000437606"
FT DOMAIN 593..669
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2090..2164
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 90..474
FT /note="Adenylation 1"
FT /evidence="ECO:0000255"
FT REGION 695..989
FT /note="Condensation 1"
FT /evidence="ECO:0000255"
FT REGION 1155..1562
FT /note="Adenylation 2"
FT /evidence="ECO:0000255"
FT REGION 1681..1776
FT /note="Methyltransferase"
FT /evidence="ECO:0000255"
FT REGION 2261..2409
FT /note="Condensation 2"
FT /evidence="ECO:0000255"
FT MOD_RES 627
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2124
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2559 AA; 283059 MW; A24D2EC2B096CB17 CRC64;
MAVSYTNFTN LPAKLYLVYR ACTFTPLHAE NLASNITQAM KQLLAQPDAC VKDIDIFSPF
NEITVSRWNA EIQEAPDASL LEVIRGHSRY RPSHTAIHAW DGTVSYSELD VTSTKWAIYL
QSQGVKAGCL VPIMMDHSKW AVIGQLAILK AGGAFVPLDP GQPLFRLENI VRLTTESHIS
LSSPHLANRL HGLVETVLVI SDERTESLPK ANAHHDAADI SPVVNNGPAY VLFTSGSTGR
PKGCVVGYGA LSDVVNQTTA LKIGPDSRVL QFASYTYGMS LIEIYCTLAA GATICVPSED
DRLNALSSIL LSMQVTWAIL TPSTTISIAD AVVCLNTLVV AGEALTMDRL HSLADKTEVI
QAFGLTEWAG ICCVSQRITS ETDLRVIGRS HTARLRLVDP ANYNRLAPVG AVAELLIEGP
AMADGYLGDP EQTARAFPKT STGGRFYRTG DLVQYAADGS LRYVSRKDSQ VKIRGMRVEL
TEVEYQIRRA FPGVEEVVVE AAAPKNSSGI PILVAFLCPE DLSGLVCTIK ETMKRSLPDY
MRPSVYVPLE FIPKTISRKV DRKALRHLVQ SSTRHELERY TQASLPSLVG PRTNIEQLVH
ELVADMLRLD PLSLGMRQNF ISLGGDSVTA MLLVNKLRRK GYKITVAAIL RAQSLLDVAS
LVHYPAGLEP SAQKSTPGDL KLVPRAIHRI SDSGTVEQSF SQARIWFLQT LRPSSTWLLL
PSATRLRGSL RVDALETAFS ALVERHETLR TTFEDREGSG VQVVAPFHPY QLEIIEIPSG
SDADLITALH GQQIRPMDLT KECWRATLFR LSPDEHVLNI VLHHIICDGW SFDIFLKTLQ
IYYAAALQGH SPLEGVEPLP IQYRDFSIWQ RQNKARTSVE QLAYWVRQLD GSQPAEFLCD
KKRPHMLSGK AGSQPVKIDV CLYHDVKRFC SMKHVTPFTV LFAAFRATHY RLTGASDATI
GIPSVSRPQA ELEELIGYFG NVQCIRTKVE SCSSSFQLLV HQVQSSITAA FENQDVPFDQ
IVSKLLKDRD VSRHPLVQVA FILHTQAQFG KLRLEGLESE QLPLPHVSRL DLEFHLYPGE
GGGDLQGEVL YSMDLFHAET INAMVLVFYD ILREGIRKPD TSIDSLPFPG GYSILNERGL
IYPQQSRSLS IIDLFDEQVR AQTDEVAVKD INGHLTYSEL HKRSSMLSAW LKNSYSFAEE
TPVGVYASRS CESIVAILGI LRAGLAYIRL DIDAPKARTE MILSCLPNCR LVLVASGLEP
PRVCVQGVQF AYIADSCKET VTDVHDFLKT CTPPGPMSLA YIVFTSGTTG TPKGVMIEHH
GVANLAKEPD IIAHAVNSRI ASHMLNPSFD ASGFEIYATL LNGGTLVCID NSVVFDFPAL
GATFIQHGIR RAFMTPAILK QTLASCNSLL RMLDILYVGG DKLDPGDVAK VQRLTTGRVQ
IFNCYGPTEN SIVSTKYRVP VDEEGVNGVP IGRSISNIGA YVVDRSLRLL PLGVLGELVV
TGPALARGYI DPKHDIGRFI ELDISEEVAP MRAYRTGDMV RYRPRDAQLE FFGRMDQQVK
VRGYRVELAE IDNTLLLSPF ISAAVTVARQ DQELVSFVTV SDMASGFNDR AETEHVDSWL
DVVEGEDYYG SVGTIEPHSL GADFLGWISM YDGEPIDKND MREWLQDTIT AILSCSPSSV
LEIGTGSGMI LFNIIGSIQK YVGLEPSPRA VDFVRRAVHW VPEAAGKVNI KCGTASDIGR
LQDMGTLDLA VINSVAQYFP SLDYLRNTIK DLVRQGVKSI FLGDIRSYAL YQEFQVSKVL
RLYGRGLTIT RFRQHMAEIA RLEKELLVDP AFFTSLPAEL PGMIEHVEIW PKRMKATNEL
SCYRYTAVLH VKRAEQPLLI REVKEISWAD FQAKGWDYNS LSQMLEISDA STVLAVENIP
FKKTIVERDM VRLLQELPED TGSVSWSSNA RGPKRALAPI DLFDVAKKTG WDIEISWARQ
RSQRGGLDAV FHRQGPRVLF RFPVDPYIPG ACSNDPLSPQ RNRLLEKHLL EYMSTKLPTY
MVPKLIHVLD KMPINNIGKV DRHVLAQRAA ITSATISESE SLFRREIEPA FTSEIERAVW
EEFTGVLGRE VGVADSFFRN GGHSLMAIRL VSRINKRLSS ALSVSELFRY PTVSGLAQHL
QGLGALETRA VTVYAPFSLL DRPYDPSEVR LPPEADIVDV TPVTECQAWF LQCWSLVSHS
FIIHGVLDVD RLRAACQAVV RHHPPLRTVF TEFQTQLVQA FDGVSLSAIL YDIARAYGNS
ASPLSNAVPF SHHLHMCRST RPDALAFWKA YLRDAVLTEV PRPEEVNATN EKPLEIIQQE
ALGEVSLPST VDITFSTLVN AAIALALARL VQRNDVIFAC VMTSRGVLAE LAESVVGPCV
NRCLLRVKVP DDSNPDSTAL DFCRNLRDNQ AQVSGHGHLG FRDVVENCTS WASLGVDVGR
IAFVTHLPAE TALETFSLTL LDSPVSYDST NVTINPGNQI LVRSAITDEQ QACIQVLSSS
NVMGAEKALF LANRILMIAQ RLSVSVSGGR SPRLLELDK
