OPAC_ASPUT
ID OPAC_ASPUT Reviewed; 462 AA.
AC A0A0C1BV72;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-2015, sequence version 1.
DT 03-AUG-2022, entry version 21.
DE RecName: Full=FAD-dependent monooxygenase opaC {ECO:0000303|PubMed:33004788};
DE EC=1.-.-.- {ECO:0000269|PubMed:33004788};
DE AltName: Full=Oxepinamide F biosynthesis cluster protein C {ECO:0000303|PubMed:33004788};
GN Name=opaC {ECO:0000303|PubMed:33004788}; ORFNames=HK57_00063;
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, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, DISRUPTION
RP PHENOTYPE, 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: FAD-dependent monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of oxepinamides, derivatives of anthranilyl-
CC containing tripeptides that share an oxepin ring and a fused
CC 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 -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:A6T923};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.43 mM for protuboxepin K {ECO:0000269|PubMed:33004788};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:33004788}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of both oxepinamide F
CC and oxepinamide E and leads to the accumulation of protuboxepin A.
CC {ECO:0000269|PubMed:33004788}.
CC -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; JOMC01000153; KIA75456.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A0C1BV72; -.
DR SMR; A0A0C1BV72; -.
DR EnsemblFungi; KIA75456; KIA75456; HK57_00063.
DR Proteomes; UP000053475; 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; Glycoprotein; Membrane; Monooxygenase; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..462
FT /note="FAD-dependent monooxygenase opaC"
FT /id="PRO_0000452995"
FT TRANSMEM 14..34
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 43..44
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 245..247
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 322
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 332..336
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT CARBOHYD 10
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 60
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 462 AA; 50577 MW; D7A079DB57061C03 CRC64;
MTVPQYIGPN RTGITVIIIG LGIGGLTAAI SCHLQGHHVI GFDKLENLEP YGDGLILTPN
GSQVLRDLDD TGAIAAWINT WAYNCRDCKI YNTDGVHVGQ HPIPDTDKGL SLLPRGGLVQ
ILYQTAKRLG LDLRLGVKIN EFVEDVDQAR VIIDGVHVQG DCIIFADGAN SRGREAVSSC
NVKPYYSGFS VYRGRADGAA LIKDPQCHWL LSKEGAIDQA TGFAGPEMYV QLATCGGGQA
SFCIGITQRF ALQHTQSAEN FWTTPIDKNE MLDKISYWKC INQIRPVIDK MAKDQFILCP
LLRAGVLDSW VSPIGRIAVI GDAAHPFFPT SAQGAAQAIE DAATLAITLA LAGKNNIRLG
LKAMEAMRKH RATYIQRNAW RVNDAWFGSP VEERIGEKAA PAIGVIDWIT EHCCRTYASN
EFDRVQDSIA TGQPYVPTNI PSQQFKEAAE WIANRNDEKE KN
