CCTP_TALIS
ID CCTP_TALIS Reviewed; 997 AA.
AC A0A0U1LSP0;
DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT 17-FEB-2016, sequence version 1.
DT 03-AUG-2022, entry version 26.
DE RecName: Full=Phenylalanine aminomutase (L-beta-phenylalanine forming) {ECO:0000303|PubMed:26954535};
DE Short=PAM {ECO:0000303|PubMed:26954535};
DE EC=5.4.3.10 {ECO:0000305|PubMed:26954535};
DE AltName: Full=Cyclochlorotine biosynthesis protein P {ECO:0000303|PubMed:26954535};
GN Name=cctP {ECO:0000303|PubMed:26954535}; ORFNames=PISL3812_02621;
OS Talaromyces islandicus (Penicillium islandicum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Trichocomaceae; Talaromyces;
OC Talaromyces sect. Islandici.
OX NCBI_TaxID=28573;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 26535 / WF-38-12;
RX PubMed=26197417; DOI=10.1016/j.jbiotec.2015.07.004;
RA Schafhauser T., Wibberg D., Rueckert C., Winkler A., Flor L., van Pee K.H.,
RA Fewer D.P., Sivonen K., Jahn L., Ludwig-Mueller J., Caradec T., Jacques P.,
RA Huijbers M.M., van Berkel W.J., Weber T., Wohlleben W., Kalinowski J.;
RT "Draft genome sequence of Talaromyces islandicus ('Penicillium islandicum')
RT WF-38-12, a neglected mold with significant biotechnological potential.";
RL J. Biotechnol. 211:101-102(2015).
RN [2]
RP FUNCTION.
RX PubMed=26954535; DOI=10.1111/1462-2920.13294;
RA Schafhauser T., Kirchner N., Kulik A., Huijbers M.M., Flor L., Caradec T.,
RA Fewer D.P., Gross H., Jacques P., Jahn L., Jokela J., Leclere V.,
RA Ludwig-Mueller J., Sivonen K., van Berkel W.J., Weber T., Wohlleben W.,
RA van Pee K.H.;
RT "The cyclochlorotine mycotoxin is produced by the nonribosomal peptide
RT synthetase CctN in Talaromyces islandicus ('Penicillium islandicum').";
RL Environ. Microbiol. 18:3728-3741(2016).
CC -!- FUNCTION: Phenylalanine aminomutase; part of the gene cluster that
CC mediates the biosynthesis of the mycotoxin cyclochlorotine, a
CC hepatotoxic and carcinogenic cyclic chlorinated pentapeptide
CC (PubMed:26954535). Cyclochlorotine is formed by the nonproteinogenic
CC amino acids L-2-aminobutyrate (2Abu), L-beta-phenylalanine (beta-Phe),
CC the unique L-cis-3,4-dichloroproline Pro(Cl(2)) and two L-serines (Ser)
CC (PubMed:26954535). The condensation of the 5 building blocks is
CC performed by the cyclochlorotine synthetase cctN, a nonribosomal
CC peptide synthetase (PubMed:26954535). The assembled linear pentapeptide
CC is then assumed to be released through cyclization by the terminal
CC condensation-like domain of cctN (PubMed:26954535). Incorporation of
CC the alternative substrates allo-threonine or alanine by the domains A3
CC or A1 respectively may lead to the production of the variants hydroxy-
CC cyclochlorotine and deoxy-cyclochlorotine, respectively
CC (PubMed:26954535). CctP probably acts as a phenylalanine aminomutase
CC and provides the uncommon building block beta-Phe (PubMed:26954535).
CC Furthermore, 2Abu can be synthesized from threonine by one of the
CC threonine dehydratases and transaminases localized outside of the
CC cluster (PubMed:26954535). The biosynthesis of the unusual
CC dichloroproline moiety remains elusive since the actual halogenase
CC still awaits to be detected, with the possibility that proline
CC halogenation is accomplished by a so far unknown type of halogenase
CC (PubMed:26954535). Finally, the cluster encoded transporters cctQ and
CC cctS are most likely responsible for cyclochlorotine secretion and
CC thereby may contribute to intrinsic resistance (PubMed:26954535). The
CC functions of the remaining proteins encoded by the cluster (cctM, cctO,
CC cctR and cctG) have not been identified yet (PubMed:26954535).
CC {ECO:0000269|PubMed:26954535}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-phenylalanine = L-beta-phenylalanine; Xref=Rhea:RHEA:34395,
CC ChEBI:CHEBI:58095, ChEBI:CHEBI:67158; EC=5.4.3.10;
CC Evidence={ECO:0000305|PubMed:26954535};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:26954535}.
CC -!- PTM: Contains an active site 4-methylidene-imidazol-5-one (MIO), which
CC is formed autocatalytically by cyclization and dehydration of residues
CC Ala-Ser-Gly. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the PAL/histidase family. {ECO:0000305}.
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DR EMBL; CVMT01000002; CRG85574.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A0U1LSP0; -.
DR SMR; A0A0U1LSP0; -.
DR STRING; 28573.A0A0U1LSP0; -.
DR EnsemblFungi; CRG85574; CRG85574; PISL3812_02621.
DR OrthoDB; 923557at2759; -.
DR BRENDA; 5.4.3.10; 4619.
DR Proteomes; UP000054383; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:InterPro.
DR GO; GO:0016841; F:ammonia-lyase activity; IEA:InterPro.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IEA:InterPro.
DR GO; GO:0043386; P:mycotoxin biosynthetic process; IEA:InterPro.
DR CDD; cd00332; PAL-HAL; 1.
DR Gene3D; 1.10.274.20; -; 1.
DR Gene3D; 1.10.275.10; -; 1.
DR InterPro; IPR001106; Aromatic_Lyase.
DR InterPro; IPR024083; Fumarase/histidase_N.
DR InterPro; IPR008948; L-Aspartase-like.
DR InterPro; IPR022313; Phe/His_NH3-lyase_AS.
DR InterPro; IPR005922; Phe_NH3-lyase.
DR InterPro; IPR023144; Phe_NH3-lyase_shielding_dom_sf.
DR InterPro; IPR021765; UstYa-like.
DR PANTHER; PTHR10362; PTHR10362; 1.
DR Pfam; PF00221; Lyase_aromatic; 1.
DR Pfam; PF11807; UstYa; 1.
DR SUPFAM; SSF48557; SSF48557; 1.
DR TIGRFAMs; TIGR01226; phe_am_lyase; 1.
DR PROSITE; PS00488; PAL_HISTIDASE; 1.
PE 3: Inferred from homology;
KW Isomerase; Reference proteome; Virulence.
FT CHAIN 1..997
FT /note="Phenylalanine aminomutase (L-beta-phenylalanine
FT forming)"
FT /id="PRO_0000438670"
FT ACT_SITE 79
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q8GMG0"
FT BINDING 232
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8GMG0"
FT BINDING 325
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8GMG0"
FT MOD_RES 178
FT /note="2,3-didehydroalanine (Ser)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10122"
FT CROSSLNK 177..179
FT /note="5-imidazolinone (Ala-Gly)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 997 AA; 109350 MW; E1C1522DF1873827 CRC64;
MASQSAHLVK THQLWELLRH RTKTGSYELD GDSLHIADVV ATAQQTSTPR LSEDPKVIKG
LQDSVDVLFD HLAKGWYVYG VNTGFGGSAD SRTTEVIELQ KALMQLTQTG ILTTPSDGSA
IPGHSTPFEW VRAAMVVRCN ASLRGHSAVS LPIIKAIINL LVHGLTPVVP LRGTVSASGD
LMPLAYVTGS IEGNPDTLLE KNGKVLPSPK ALQEAGLAPV FLGPKEGLGL INGTASSAGL
GALVVAQAHS LAFLTQVLTG GAVEALRGSS ESFHPFIARA RPHPGQIECA RNIAYFLRGS
HLSRDVLAPK DRRREDLAQD RYSLRSAPQW IGPQLEDLLL ADQQISIELN SSCDNPLVDS
ETNDIYYGCN FQAAAVTSAM EKVRLAMQMF GRMLFAQSTE MIDVHLSGGL PANLAADNPS
ISFTMKGVDI NMAAYMAELS YLANPMSSHV QAAEMHNQSV NSMAFASARI SHDAIDVLTK
MCACSVFTVC QALDLRALHM AFIADATKAL ASTIELKFSA KVEAGQLNSL QMLIQAHVTR
AWGLTGKLDL HARCESLIDS ALPIVLCHVA GDVADIIEWK TQAIEVVWNV WTNTFASFSA
APHTSQLLGA GSRLLYNFVR KTLGVPFHEG FVEHPTADSQ TLHSRPKKTI DILANLSDSS
NSKRDIERER LKGEKPTRSI LITMEGKTSR YQDEAHDSAG SFNEETEGLM SGLHRSTKKR
KLSSIVKLAT PFLIVSFILN IVQLAYITVR RPECYSLYAK LKEHEITVPF RYATEYSDDE
HTHEEKDALW NAIDISEGFV AISNDESDRL GLPRSKTFPW DANKGIYVSH GHHALHCTVL
LHAYTYDAHQ GKKPLVSYHH IEHCLDLLRQ DIMCYANDVM DYTPDHGDNF LTGEGQQRKC
RDWNKLSAWV KERSACYKTI NITRAGEDHG VAHQLDRYTY CPPGSPYEPL IKAFKDLGRV
NTGNLAADGF HELTPEELAA EAQAVAEHNK QILADEG
