USTC_ASPFN
ID USTC_ASPFN Reviewed; 403 AA.
AC B8NM64;
DT 05-OCT-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 54.
DE RecName: Full=Cytochrome P450 monooxygenase ustC {ECO:0000303|PubMed:24841822};
DE EC=1.-.-.- {ECO:0000305|PubMed:27166860};
DE AltName: Full=Ustiloxin B biosynthesis protein C {ECO:0000303|PubMed:24841822};
DE Flags: Precursor;
GN Name=ustC {ECO:0000303|PubMed:24841822}; ORFNames=AFLA_094960;
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, DISRUPTION PHENOTYPE, AND CATALYTIC ACTIVITY.
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: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of the secondary metabolite ustiloxin B, an
CC antimitotic tetrapeptide (PubMed:24841822, PubMed:27166860,
CC PubMed:26703898). First, ustA is processed by the subtilisin-like
CC endoprotease Kex2 that is outside the ustiloxin B gene cluster, at the
CC C-terminal side of Arg-Lys, after transfer to Golgi apparatus through
CC the endoplasmic reticulum (ER) (PubMed:24841822). Cleavage by KEX2
CC generates 16 peptides YAIG-I to YAIG-XVI (PubMed:24841822). To process
CC the precursor peptide further, at least two peptidases are necessary to
CC cleave the N-terminal and C-terminal sides of the Tyr-Ala-Ile-Gly core
CC peptide which serves as backbone for the synthesis of ustiloxin B,
CC through cyclization and modification of the tyrosine with a non-protein
CC coding amino acid, norvaline (PubMed:24841822). One of the two
CC peptidases must be the serine peptidase ustP; and the other pepdidase
CC is probably ustH (PubMed:24841822). Macrocyclization of the core
CC peptide derived from ustA requires the tyrosinase ustQ, as well as the
CC homologous oxidases ustYa and ustYb, and leads to the production of the
CC first cyclization product N-desmethylustiloxin F (PubMed:27166860,
CC PubMed:26703898). For the formation of N-desmethylustiloxin F, three
CC oxidation steps are required, hydroxylation at the benzylic position,
CC hydroxylation at either the aromatic ring of Tyr or beta-position of
CC Ile, and oxidative cyclization (PubMed:27166860). UstQ may catalyze the
CC oxidation of a phenol moiety, whereas the ustYa and ustYb are most
CC likely responsible for the remaining two-step oxidations
CC (PubMed:27166860). N-desmethylustiloxin F is then methylated by ustM to
CC yield ustiloxin F which in turn substrate of the cytochrome P450
CC monooxygenase ustC which catalyzes the formation of S-deoxyustiloxin H
CC (PubMed:27166860). The flavoprotein monooxygenases ustF1 and ustF2 then
CC participate in the modification of the side chain of S-deoxyustiloxin
CC H, leading to the synthesis of an oxime intermediate, via ustiloxin H
CC (PubMed:27166860). Finally, carboxylative dehydration performed by the
CC cysteine desulfurase-like protein ustD yields ustiloxin B
CC (PubMed:27166860). {ECO:0000269|PubMed:24841822,
CC ECO:0000269|PubMed:26703898, ECO:0000269|PubMed:27166860}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:24841822}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of ustiloxin B but
CC accumulates intermediates such as ustiloxin F and C (PubMed:24841822,
CC PubMed:27166860, PubMed:26703898). {ECO:0000269|PubMed:24841822,
CC ECO:0000269|PubMed:27166860}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; EQ963480; EED49415.1; -; Genomic_DNA.
DR RefSeq; XP_002381316.1; XM_002381275.1.
DR AlphaFoldDB; B8NM64; -.
DR SMR; B8NM64; -.
DR EnsemblFungi; EED49415; EED49415; AFLA_094960.
DR VEuPathDB; FungiDB:AFLA_094960; -.
DR eggNOG; KOG0157; Eukaryota.
DR HOGENOM; CLU_001570_14_0_1; -.
DR OMA; RVIFHIS; -.
DR Proteomes; UP000001875; Unassembled WGS sequence.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR Gene3D; 1.10.630.10; -; 2.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..403
FT /note="Cytochrome P450 monooxygenase ustC"
FT /id="PRO_0000437300"
FT BINDING 318
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CARBOHYD 52
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 92
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 403 AA; 46402 MW; 0E57569A8F9DB317 CRC64;
MSPFIFAVTL TFAILALGIL RRRYFHPLSR FPGPFLGSVT SLYQTYWHVH PNKTLHDTEL
HRKYGPIVRY SPNGLIVNDP ALLPVIYNRR ANKTDFYAPV FDTHSTFTRK DYREHVASRK
AISHAVGFLA FFRTEYSYGL VLLMIIFKQY SVTNTRLFEP QVDGILSELA GSSVTPSQLA
RVIFHISRNF KVQEKLYEEL VAAEQDGRIP PLSAIISDEQ AHRLPFLSAC IREAQRYAPT
MSQLPRYAPE GTGLELHEQY VPPGTSVSTS PWIIGRNKDL YGEDANSFRP ERWLEASPEE
ERRWDHFSFH FGYGARKCLA NNFGLMQLYK VAAEVCAYPI RCLLRYRAHH ECRYFVVLKL
KLKGRTRIQS VEGRLRVPGF ALIAEQDPGH KHNGYINMDL FRA
