USTD_ASPFN
ID USTD_ASPFN Reviewed; 439 AA.
AC B8NM72;
DT 05-OCT-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Cysteine desulfurase-like protein ustD {ECO:0000303|PubMed:24841822};
DE EC=2.-.-.- {ECO:0000305|PubMed:27166860};
DE AltName: Full=Ustiloxin B biosynthesis protein D {ECO:0000303|PubMed:24841822};
GN Name=ustD {ECO:0000303|PubMed:24841822}; ORFNames=AFLA_095040;
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: Cysteine desulfurase-like protein; part of the gene cluster
CC that mediates the biosynthesis of the secondary metabolite ustiloxin B,
CC an 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=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:P0A6B9};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:27166860}.
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:26703898, ECO:0000269|PubMed:27166860}.
CC -!- SIMILARITY: Belongs to the class-V pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
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DR EMBL; EQ963480; EED49423.1; -; Genomic_DNA.
DR RefSeq; XP_002381324.1; XM_002381283.1.
DR AlphaFoldDB; B8NM72; -.
DR SMR; B8NM72; -.
DR STRING; 5059.CADAFLAP00009189; -.
DR EnsemblFungi; EED49423; EED49423; AFLA_095040.
DR VEuPathDB; FungiDB:AFLA_095040; -.
DR eggNOG; KOG1549; Eukaryota.
DR HOGENOM; CLU_003433_2_2_1; -.
DR OMA; TCNHVSN; -.
DR Proteomes; UP000001875; Unassembled WGS sequence.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR000192; Aminotrans_V_dom.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR Pfam; PF00266; Aminotran_5; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
PE 1: Evidence at protein level;
KW Pyridoxal phosphate; Transferase.
FT CHAIN 1..439
FT /note="Cysteine desulfurase-like protein ustD"
FT /id="PRO_0000437301"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 120..121
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT BINDING 206
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:O29689"
FT BINDING 255..257
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT MOD_RES 258
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
SQ SEQUENCE 439 AA; 48278 MW; 1B749C0DD4881AD0 CRC64;
MKSVATSSLD DVDKDSVPLG SSINGTAQAE TPLENVIDVE SVRSHFPVLG GETAAFNNAS
GTVVLKEAIE STSNFMYSFP FPPGVDAKSM EAITAYTGNK GKVAAFINAL PDEITFGQST
TCLFRLLGLS LKPMLNNDCE IVCSTLCHEA AASAWIHLSR ELGITIKWWS PTTTPNSPDD
PVLTTDSLKP LLSPKTRLVT CNHVSNVVGT IHPIREIADV VHTIPGCMLI VDGVACVPHR
PVDVKELDVD FYCFSWYKLF GPHLGTLYAS RKAQDRYMTS INHYFVSSSS LDGKLALGMP
SFELQLMCSP IVSYLQDTVG WDRIVRQETV LVTILLEYLL SKPSVYRVFG RRNSDPSQRV
AIVTFEVVGR SSGDVAMRVN TRNRFRITSG ICLAPRPTWD VLKPKSSDGL VRVSFVHYNT
VEEVRAFCSE LDEIVTRDT
