ID USTP_ASPFN Reviewed; 480 AA.
AC B8NM69;
DT 05-OCT-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 27-MAR-2024, entry version 59.
DE RecName: Full=Peptidase S41 family protein ustP {ECO:0000303|PubMed:24841822};
DE EC=3.4.-.- {ECO:0000305|PubMed:24841822};
DE AltName: Full=Ustiloxin B biosynthesis protein P {ECO:0000303|PubMed:24841822};
GN Name=ustP {ECO:0000303|PubMed:27166860}; ORFNames=AFLA_095010;
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, DISRUPTION PHENOTYPE, AND CATALYTIC ACTIVITY.
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: Peptidase S41 family protein; 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 -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:26703898}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of ustiloxin B and its
CC intermediate ustiloxin F (PubMed:24841822, PubMed:26703898).
CC {ECO:0000269|PubMed:24841822, ECO:0000269|PubMed:26703898}.
CC -!- SIMILARITY: Belongs to the peptidase S41A family. {ECO:0000305}.
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DR EMBL; EQ963480; EED49420.1; -; Genomic_DNA.
DR RefSeq; XP_002381321.1; XM_002381280.1.
DR AlphaFoldDB; B8NM69; -.
DR STRING; 332952.B8NM69; -.
DR EnsemblFungi; EED49420; EED49420; AFLA_095010.
DR VEuPathDB; FungiDB:AFLA_009737; -.
DR eggNOG; ENOG502S18W; Eukaryota.
DR HOGENOM; CLU_014251_1_1_1; -.
DR OMA; VSTCAFF; -.
DR Proteomes; UP000001875; Unassembled WGS sequence.
DR GO; GO:0008236; F:serine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR029045; ClpP/crotonase-like_dom_sf.
DR InterPro; IPR005151; Tail-specific_protease.
DR PANTHER; PTHR37049:SF4; CHITIN-BINDING TYPE-2 DOMAIN-CONTAINING PROTEIN; 1.
DR PANTHER; PTHR37049; PEPTIDASE S41 FAMILY PROTEIN; 1.
DR Pfam; PF03572; Peptidase_S41; 1.
DR SUPFAM; SSF52096; ClpP/crotonase; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Protease; Serine protease.
FT CHAIN 1..480
FT /note="Peptidase S41 family protein ustP"
FT /id="PRO_0000437296"
FT REGION 78..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 134..336
FT /note="Peptidase S41 domain"
FT /evidence="ECO:0000255"
SQ SEQUENCE 480 AA; 52630 MW; EC06904C3F595234 CRC64;
MANVQSRYNH LFPSPAAAFS GMYTGGLWTN NLGSWPGKAN QTVEFSNGTK MTVETTASVM
LDRGLDFSSG ESLFQTACMP NKKSRPPDPR PSLAVGKPPY SIPLGGPSMY PDPIIHHKKD
FVRGYYLHEE RLEDVAVLQL PTFRLIGESP VSLARVAVQF LERARKDGKE KLIIDLSNNM
GGDINLGFNL FRILFPDKPI YTATRFPSTE LIGLMGRVFS TSQGNEAVEH DNTLDLPLVF
QNAVTPDHRH SFGSWEKLFG PVEIAGQNMS HLHATYNFTT ASTEDNPISG YGGIEFGPST
QLFHAENIII MTNGICASTC TILARLLKQQ GVRSIVFGGR PRAAPMQLLG GSKGGQYWSL
VTISHYIKKA REIAVNASGA GSPILSEDEL ARFLELAPPP LTGFPIRIDS RGGSGVNFRN
EYDEKDPTTP LQFVYEAADC RLFWTAENYV FPESSWVAAA DAMFGDASCV EESDGHHITP
//
