USTO_ASPFN
ID USTO_ASPFN Reviewed; 249 AA.
AC B8NM62;
DT 05-OCT-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 50.
DE RecName: Full=Pyridoxamine 5'-phosphate oxidase family protein ustO {ECO:0000303|PubMed:24841822};
DE EC=1.-.-.- {ECO:0000305};
DE AltName: Full=Ustiloxin B biosynthesis protein O {ECO:0000303|PubMed:24841822};
GN Name=ustO {ECO:0000303|PubMed:24841822}; ORFNames=AFLA_094940;
OS Aspergillus flavus (strain ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357
OS / JCM 12722 / SRRC 167).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=332952;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357 / JCM 12722 / SRRC
RC 167;
RX PubMed=25883274; DOI=10.1128/genomea.00168-15;
RA Nierman W.C., Yu J., Fedorova-Abrams N.D., Losada L., Cleveland T.E.,
RA Bhatnagar D., Bennett J.W., Dean R., Payne G.A.;
RT "Genome sequence of Aspergillus flavus NRRL 3357, a strain that causes
RT aflatoxin contamination of food and feed.";
RL Genome Announc. 3:E0016815-E0016815(2015).
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24841822; DOI=10.1016/j.fgb.2014.04.011;
RA Umemura M., Nagano N., Koike H., Kawano J., Ishii T., Miyamura Y.,
RA Kikuchi M., Tamano K., Yu J., Shin-ya K., Machida M.;
RT "Characterization of the biosynthetic gene cluster for the ribosomally
RT synthesized cyclic peptide ustiloxin B in Aspergillus flavus.";
RL Fungal Genet. Biol. 68:23-30(2014).
RN [3]
RP FUNCTION.
RX PubMed=27166860; DOI=10.1002/anie.201602611;
RA Ye Y., Minami A., Igarashi Y., Izumikawa M., Umemura M., Nagano N.,
RA Machida M., Kawahara T., Shin-Ya K., Gomi K., Oikawa H.;
RT "Unveiling the biosynthetic pathway of the ribosomally synthesized and
RT post-translationally modified peptide ustiloxin B in filamentous fungi.";
RL Angew. Chem. Int. Ed. 55:8072-8075(2016).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26703898; DOI=10.1016/j.fgb.2015.12.010;
RA Nagano N., Umemura M., Izumikawa M., Kawano J., Ishii T., Kikuchi M.,
RA Tomii K., Kumagai T., Yoshimi A., Machida M., Abe K., Shin-ya K., Asai K.;
RT "Class of cyclic ribosomal peptide synthetic genes in filamentous fungi.";
RL Fungal Genet. Biol. 86:58-70(2016).
CC -!- FUNCTION: Pyridoxamine 5'-phosphate oxidase family protein; part of the
CC gene cluster that mediates the biosynthesis of the secondary metabolite
CC ustiloxin B, an antimitotic tetrapeptide (PubMed:24841822,
CC PubMed:27166860, PubMed:26703898). First, ustA is processed by the
CC subtilisin-like endoprotease Kex2 that is outside the ustiloxin B gene
CC cluster, at the C-terminal side of Arg-Lys, after transfer to Golgi
CC apparatus through the endoplasmic reticulum (ER) (PubMed:24841822).
CC Cleavage by KEX2 generates 16 peptides YAIG-I to YAIG-XVI
CC (PubMed:24841822). To process the precursor peptide further, at least
CC two peptidases are necessary to cleave the N-terminal and C-terminal
CC sides of the Tyr-Ala-Ile-Gly core peptide which serves as backbone for
CC the synthesis of ustiloxin B, through cyclization and modification of
CC the tyrosine with a non-protein coding amino acid, norvaline
CC (PubMed:24841822). One of the two peptidases must be the serine
CC peptidase ustP; and the other pepdidase is probably ustH
CC (PubMed:24841822). Macrocyclization of the core peptide derived from
CC ustA requires the tyrosinase ustQ, as well as the homologous oxidases
CC ustYa and ustYb, and leads to the production of the first cyclization
CC product N-desmethylustiloxin F (PubMed:27166860, PubMed:26703898). For
CC the formation of N-desmethylustiloxin F, three oxidation steps are
CC required, hydroxylation at the benzylic position, hydroxylation at
CC either the aromatic ring of Tyr or beta-position of Ile, and oxidative
CC cyclization (PubMed:27166860). UstQ may catalyze the oxidation of a
CC phenol moiety, whereas the ustYa and ustYb are most likely responsible
CC for the remaining two-step oxidations (PubMed:27166860). N-
CC desmethylustiloxin F is then methylated by ustM to yield ustiloxin F
CC which in turn substrate of the cytochrome P450 monooxygenase ustC which
CC catalyzes the formation of S-deoxyustiloxin H (PubMed:27166860). The
CC flavoprotein monooxygenases ustF1 and ustF2 then participate in the
CC modification of the side chain of S-deoxyustiloxin H, leading to the
CC synthesis of an oxime intermediate, via ustiloxin H (PubMed:27166860).
CC Finally, carboxylative dehydration performed by the cysteine
CC desulfurase-like protein ustD yields ustiloxin B (PubMed:27166860).
CC {ECO:0000269|PubMed:24841822, ECO:0000269|PubMed:26703898,
CC ECO:0000269|PubMed:27166860}.
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:P0AFI7};
CC Note=Binds 1 FMN per subunit. {ECO:0000250|UniProtKB:P0AFI7};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:24841822}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Decreases the production of ustiloxin B
CC (PubMed:24841822, PubMed:26703898). {ECO:0000269|PubMed:24841822,
CC ECO:0000269|PubMed:26703898}.
CC -!- SIMILARITY: Belongs to the pyridoxamine 5'-phosphate oxidase family.
CC {ECO:0000305}.
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DR EMBL; EQ963480; EED49413.1; -; Genomic_DNA.
DR RefSeq; XP_002381314.1; XM_002381273.1.
DR AlphaFoldDB; B8NM62; -.
DR SMR; B8NM62; -.
DR EnsemblFungi; EED49413; EED49413; AFLA_094940.
DR VEuPathDB; FungiDB:AFLA_094940; -.
DR eggNOG; ENOG502S3ZI; Eukaryota.
DR HOGENOM; CLU_054794_1_0_1; -.
DR OMA; TISHAYE; -.
DR Proteomes; UP000001875; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 2.30.110.10; -; 1.
DR InterPro; IPR012349; Split_barrel_FMN-bd.
PE 3: Inferred from homology;
KW Flavoprotein; FMN; Membrane; Oxidoreductase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..249
FT /note="Pyridoxamine 5'-phosphate oxidase family protein
FT ustO"
FT /id="PRO_0000437306"
FT TRANSMEM 227..247
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 21..24
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P0AFI7"
FT BINDING 76..81
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P0AFI7"
FT BINDING 91..92
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P0AFI7"
FT BINDING 105
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P0AFI7"
FT BINDING 163..164
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P0AFI7"
FT BINDING 215..217
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P0AFI7"
SQ SEQUENCE 249 AA; 28357 MW; 89E0884E08863C86 CRC64;
MPIFYESLSD NLRDWALRQP LFFVSSAPYR GRHINVSPKG LPDSSFAVLS PSKVAYVDST
GSGCETICHL RENGRATVMF CSFDATPRIM RLFCTGSVIE WNDPRYAGYV KRMGVKSLVG
ARAVIILDIF KVQISCGFGV PLLDLTVDPE TNEPKPCFTN RPRLGKFAEY TINRGELPEY
QMQWNSRSLD GLPGLHSAMR DKGEFIWWAH VTNWASYYHF QLDIIKTGMA LMFLVMVVAQ
WVGYVLYQW
