OPAA_ASPUT
ID OPAA_ASPUT Reviewed; 3901 AA.
AC A0A0C1E5J8;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-2015, sequence version 1.
DT 23-FEB-2022, entry version 30.
DE RecName: Full=Nonribosomal peptide synthetase opaA {ECO:0000303|PubMed:33004788};
DE EC=6.3.2.- {ECO:0000269|PubMed:33004788};
DE AltName: Full=Oxepinamide F biosynthesis cluster protein A {ECO:0000303|PubMed:33004788};
DE AltName: Full=Quinazolinone synthase opaA {ECO:0000303|PubMed:33004788};
GN Name=opaA {ECO:0000303|PubMed:33004788}; ORFNames=HK57_00065;
OS Aspergillus ustus.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX NCBI_TaxID=40382;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND IDENTIFICATION.
RC STRAIN=3.3904;
RX PubMed=25706180; DOI=10.1371/journal.pone.0116089;
RA Pi B., Yu D., Dai F., Song X., Zhu C., Li H., Yu Y.;
RT "A genomics based discovery of secondary metabolite biosynthetic gene
RT clusters in Aspergillus ustus.";
RL PLoS ONE 10:e0116089-e0116089(2015).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, DOMAIN, AND PATHWAY.
RX PubMed=33004788; DOI=10.1038/s41467-020-18713-0;
RA Zheng L., Wang H., Fan A., Li S.M.;
RT "Oxepinamide F biosynthesis involves enzymatic D-aminoacyl epimerization,
RT 3H-oxepin formation, and hydroxylation induced double bond migration.";
RL Nat. Commun. 11:4914-4914(2020).
CC -!- FUNCTION: Nonribosomal peptide synthetase; part of the gene cluster
CC that mediates the biosynthesis of oxepinamides, derivatives of
CC anthranilyl-containing tripeptides that share an oxepin ring and a
CC fused pyrimidinone moiety (PubMed:33004788). The nonribosomal peptide
CC synthetase (NRPS) opaA assembles the quinazolinone core with D-Phe
CC incorporation (PubMed:33004788). The first adenylation domain (A1) of
CC opaA loads and activates anthranilic acid whereas the second A domain
CC (A2) is for activating of L-Phe, which is then converted to D-form by
CC the E domain (PubMed:33004788). The third A domain (A3) is responsible
CC for L-Ile activation and the terminal condensation domain C3 for
CC cyclization and releasing the NRPS product protuboxepin K
CC (PubMed:33004788). The cytochrome P450 monooxygenase opaB then
CC catalyzes alone the oxepin ring formation to convert protuboxepin K
CC into protuboxepin A (PubMed:33004788). The flavoenzyme opaC installs
CC subsequently one hydroxyl group at the oxepin ring, accompanied by
CC double bond migration, to form 15-epi-oxepinamide E (PubMed:33004788).
CC The epimerase opaE changes the D-Phe residue back to L-form, leading to
CC oxepinamide E, which is further methylated at the hydroxyl group at C-
CC 12 by the O-methyltransferase OpaF to yield oxepinamide F
CC (PubMed:33004788). {ECO:0000269|PubMed:33004788}.
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 epimerase (E) domains (responsible for L- to D- amino acid conversion)
CC are present within the NRP synthetase. OpaA has the following
CC architecture: A1-T1-C1-A2-T2-E-C2-A3-T3-C3.
CC {ECO:0000269|PubMed:33004788}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of both oxepinamide F
CC and oxepinamide E. {ECO:0000269|PubMed:33004788}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; JOMC01000153; KIA75458.1; -; Genomic_DNA.
DR SMR; A0A0C1E5J8; -.
DR EnsemblFungi; KIA75458; KIA75458; HK57_00065.
DR Proteomes; UP000053475; Unassembled WGS sequence.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR Gene3D; 1.10.1200.10; -; 3.
DR Gene3D; 3.30.300.30; -; 3.
DR Gene3D; 3.30.559.10; -; 4.
DR Gene3D; 3.40.50.12780; -; 3.
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; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR Pfam; PF00501; AMP-binding; 3.
DR Pfam; PF00668; Condensation; 4.
DR Pfam; PF00550; PP-binding; 3.
DR SMART; SM00823; PKS_PP; 3.
DR SUPFAM; SSF47336; SSF47336; 3.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 2.
DR PROSITE; PS00455; AMP_BINDING; 3.
DR PROSITE; PS50075; CARRIER; 3.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
PE 1: Evidence at protein level;
KW Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..3901
FT /note="Nonribosomal peptide synthetase opaA"
FT /id="PRO_0000452993"
FT DOMAIN 780..854
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1858..1936
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3375..3451
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 248..641
FT /note="Adenylation 1"
FT /evidence="ECO:0000250|UniProtKB:Q4WLW5, ECO:0000255"
FT REGION 891..1164
FT /note="Condensation 1"
FT /evidence="ECO:0000250|UniProtKB:Q4WLW5, ECO:0000255"
FT REGION 1328..1725
FT /note="Adenylation 2"
FT /evidence="ECO:0000250|UniProtKB:Q4WLW5, ECO:0000255"
FT REGION 1953..2261
FT /note="Epimerase"
FT /evidence="ECO:0000250|UniProtKB:Q4WLW5, ECO:0000255"
FT REGION 2403..2826
FT /note="Condensation 2"
FT /evidence="ECO:0000250|UniProtKB:Q4WLW5, ECO:0000255"
FT REGION 2846..3243
FT /note="Adenylation 3"
FT /evidence="ECO:0000250|UniProtKB:Q4WLW5, ECO:0000255"
FT REGION 3509..3837
FT /note="Condensation 3"
FT /evidence="ECO:0000250|UniProtKB:Q4WLW5, ECO:0000255"
FT MOD_RES 815
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1895
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3412
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3901 AA; 433379 MW; 849E1DCCDC2A82BE CRC64;
MAIGNDELLA SHEEHSRCQF PRLVANPSEE KCLRCNLDVP IRNLLKEACA QYETSLDYVL
GAIWAIILHQ YIQDDYVGFA VVRRTRTGEA EAEFTDSAER SYSWRTPIHG EMAIGELIKP
STWKRSPYAP GVDLFNTSLV IEEEQQQEQT NTGHHVLKEP FQISLLVKCW PDSPVISLVF
SSSYLHPTFG KALASSIEQC ARGILSCHDS LVNQMNLFSP IQREIMTRWQ GVPSLTSHFN
FLYEIVCHNA QHHPSVVALD AWDGRWSYQE LDEATSRLAA RLVTHGVGPG VFVPVCFDKS
CWAVVAMLAI NKAGAAFVPI DPSYPAERRQ MIILTVAASV ILTSQQHLNL FPPSPEVMTI
CLSPSILSDS PASGYPRRMR FEGPAYVLFT SGSTGEPKGC EISHQAFASL VNHTEDLHLT
PESRTLQFAS YSFGMSVIEI FCTLVAGGTV CIPSAEQRLN DLATAIKTME INWAILTPTV
IASLYPEDLP HLRFVLVAGE ISDQSAVDQW AAAGVDIRHA YGLTEWTGIF AVSHKISGQG
TGQTTIGKPV DAHAWLVNTQ NPAQLVPLGA PGELVIKGPG LARGYLHDPL RTKASFLSDL
PWLAEWKLAH GQVYRTGDIM RYHVDGSLVY LHRKDNQIKI RGLRVELGEI ESHLTRILKG
AKRVAVIACK PKGSHDLHVL IALILLPHVA DGQLLAIGRR SKGLPFVQLP GKTREELRDA
RESLRRWLPD YMIPQFLLPL VDMPTTVSGK IDRRRIRTLL NELSVKELMN HAGVQVEHRL
PVTANEIVVH EVTCKSLGLD LVSMQDSFFD LAGDSVAAMK MSGLARQHGL QLTVKDIFEA
PILQDMATRL TRIKELTVTA IPFALLPNVV PSQIVAEIAE QAKVDPLEIT DAYPCSALQE
GLCALSMRDA QSYKVRLICH IRPGTDLQVF RAAWERTYLI NDVLRTRFVT SSTHGAIQAV
IQRPFRWDEA ESFEQYVTLI EQEPMGLGKQ LVRACLLRDP RSQHQQTAFV LTLHHGICDR
WSIRQLLEQI DRQVHAFPKQ LELDPIEFRP FISYITETAS KSAEYWENQF QDIKAVIFPE
LPAPDYTPVA DQLTQYDIKL PTRLVREISI ANYIRLAWAL VLAHNTSSDD VVFGAIVSGR
ASPVKGIVTL TGPTIATVPI RINLSREMTV LQALTSVERQ FIEMLPWEQA GLQNIRRLSP
EADRACSFQS LFTVQPFLGN PPPLFSACEE GAAIAGGFAS YALNIECYIS EDERRMQAKV
AFDPRVIALG RVRRLLEHLQ VVLNEVAAQT ERRLSSISPL SPSDMSLLWE WNKSVPPKPK
ELLHEIIQSH AQKTPKSPAV SAFDGELTFE ELEWHATQLA GELLQQVPHP GMLLPMLFEK
SVWVTVAMLA VLKIGSAIVL LDGSYSIERM RTICADVEAP LVVCSSQMTS TVEQIGLRPV
IVAHTRAFFS KSASPVSLPP VRVHSDSPCY MIFTSGSTGM PKGLLVNHGA FAASMLGWMP
KLQVDKSSRV LQFSSFAFDA CFAETFTALF AGACICVPSD DQRMNDLHAA MRQHRISHAI
LTPSSARVVR AEQVPSLRVL ALVGEPILPS DMAYWAPRVR LLNGYGPAEC APASVVQYID
GSPALDVRDI GHPVGCVAWV CDPRDSEILK PVGVAGELLI EGPNVGLGYF KDAAKTDSAF
VQPRWLQSLR GMTGVRAYRS SDLVCYTEDG RLRYLGRIGN QVKLRGQRLD PTHIEHQLAR
CFPGATEVAV VVGCPRNASD RPTLAAFVVV DKKANGNGST DFHDVPTKDV ANRAATARAR
MQQVLPGYMV PTLMIPVSSL PCSAAGKLDR RALENEIASR TWKELSQYES ANESSTNRTP
LDTERDLQGI WAKVLDLPME AVGLRQSFFA LGGDSITAML VVAEARGRRV GLNITVDDIF
RFRTIEQIAA QAATRAATIQ QLCSHDVLDV PFKLTPIQQL FFRTQGQKVR HRFNHNVLLH
LTQRIPYHRL ESAMKTIVTA HPMLRARFVP GTAGLDWKQN IPSNIEGTFR CKHQTNGTMA
RILADGQRSL NITAGPVFSA DLIDTEERQT ILLVAHHLVV DLVSWTVILN DLDELLCGDP
ISGHTSTSFQ TWSRLLDEYV RGQARAARLP DAQPWDGIEG FWGISQEQMT FGSCEDTTVQ
IERETTDLLL GDVNKTFGTQ PVEVLHAALL FAFIQAFPKR PPPATYSEAH GREPWDATTD
LTRTVGWFTT LAPVLLQLDS ASELSEAVGQ VKDARRRLTR NGLDAFTNRQ QAGVMEIVFN
YGGRYSQQLQ KAGALFEVQS FQTLNIFDTG LDVRRWSVVD INSFVQDGKL TFVFTHPCGP
SQTRIISEWT LHLMKTLKTL ATDFSSASRI YTPMDFPLLK TDKAQLERLL SSLSWISPAS
DIENLYPCAP IQRGILLSQE KERSHYHVTM LWEIQIAGGV SASVPKAKDA IHQVITCHPC
LRTSFVRSFS ERALYDQVVT HNASPQIEVV HNPSKGWQGR PSAKGSPLTP EFPNRFTIHV
DQEQRVYIRL DVTHALVDAM SFSLIQRDLC LAYEGRLNIS SGPPYANFIA YLQSRNEEED
RVFWEEELEG IQPCLFPSLT DYQVGEVDDA LSWSVELQHS EEIYAYCRAH SVTPANIFCL
AWSLVLRSYV GSDDVCFGVL ASGRELPFEG AQDVVGPLIN VLTFRNRLKE NLSVGECLQQ
VHTKYLRYLQ HQTYPLADIS HQKGDAVLFN TALSIQRVMV SADTPTSTSL NLVHRRDPVE
YAIAINVDME PSRIAVHLRY WLSSLSSEMA MLIASSFEQA VHQIITNDQL HPAQLDLVST
DHKRLLHRWN STLPAFDEAP IHETIQQHVR ETPDALAVRW SKGSFTYREL GLLSDRLGGH
LRRQGVAPGA FVPLCFDKSP WTVVALLAVI KSGAAFALCD VTHPDSRLRS ICQDLQSTVI
LCSPDQETRC KKIAEKAIVV GEHNNSWKGD TVGPPTPELS VRAPLFVVYT SGSTGKPKGV
LIEHRSFCAL VHYQISVWGM SPAARVMQFA SYAFDASVFE ILFPLMRGTC TCILTEVERR
DYLDATMKRL RVTHAFLTPS VARQLSPAAV PDLQVLVCGG EPLSHQDINQ WTVNVRLVEA
YGPAECTVFS ACQPSLTPAS CPSDIGRPVG CVVWLVDPDD TERLMPVGSL GEILIEGPIV
GRGYINNSQA TESSFIKPPA WLRAIRPDLD PTTRLYKTGD LARYFPDGRL DIHGRKDSQI
KIRGQRIELG EVEFQVQSRF KLAVGVVVDV APTGPNGSTA LCAFICFGGR VSPSEVDSQV
LRAADEDFAA EAASASAALF ECLPAYMVPS YFFPLANLPV NASGKADRRY LKSLVDIPAE
QLNQYRPLSN RQQRLPSTAG EQLLHNIWST ALGLDGKLIG ADDSFFQVGG DSVSAMKVAA
AARQQGLEIS VADIFAHPRL SALAARSRSK DASDSGFDPT PFSLCPPGAK VLLPMLLRAR
NMLPPKSTII DILPVSEGQG FFLTRVALHH FSFAVEGKLD IERIRHACET VYLFFAILRT
IFIHWHGQIL QLVLDNIEVP FHHILTDSDP AEVHRELRDL DRKVASVLDE QPPCAFILIS
DRSGTRHELI FRLSHTQWDG LSLAELFSAF GSAYHNRPIP PTTPLTTVVY HRLMRNKTKS
LSFWRDYLRG STISSLIPSA PETTDLSPGT TIWENTNLQP APEPPSGITM ASVVKAAWAL
VIAQEKGRGC RDIVFGQTVN GRSSALPNIE RIFGCCLNFI PVRIRVREEM SIYDLLRHTQ
AQYQETVAHD DVGFQSIVDE STDWPRGTYF NSIVQHQNIP LHHVMPLEDL KTHFTLNGYF
RPGREVIIFT EPDGDVLSVQ FCANPNVIEF SYAQKLHRTL VDLIVHLCRC PDDLVSTLLV
E
