CCTT_TALIS
ID CCTT_TALIS Reviewed; 283 AA.
AC A0A0U1LQE2;
DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT 17-FEB-2016, sequence version 1.
DT 03-AUG-2022, entry version 21.
DE RecName: Full=Short-chain dehydrogenase cctT {ECO:0000303|PubMed:26954535};
DE EC=1.1.1.- {ECO:0000305|PubMed:26954535};
DE AltName: Full=Cyclochlorotine biosynthesis protein T {ECO:0000303|PubMed:26954535};
DE Flags: Precursor;
GN Name=cctT {ECO:0000303|PubMed:26954535}; ORFNames=PISL3812_02625;
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: Short-chain dehydrogenase; 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 -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:26954535}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; CVMT01000002; CRG85579.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A0U1LQE2; -.
DR SMR; A0A0U1LQE2; -.
DR STRING; 28573.A0A0U1LQE2; -.
DR EnsemblFungi; CRG85579; CRG85579; PISL3812_02625.
DR OMA; EMVFAWA; -.
DR OrthoDB; 1313182at2759; -.
DR Proteomes; UP000054383; Unassembled WGS sequence.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 3: Inferred from homology;
KW Glycoprotein; NAD; NADP; Oxidoreductase; Reference proteome; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..283
FT /note="Short-chain dehydrogenase cctT"
FT /id="PRO_0000438673"
FT ACT_SITE 147
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 7..15
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 34..35
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 60..62
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 147..151
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 180..182
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT CARBOHYD 131
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 283 AA; 30356 MW; 70151C4595F17CFA CRC64;
MLKTVLITGC SHGGLGAAMA KIYHAKGFQV FATVRNKAKV GSLGGIDGIE IMELEVTSVE
SIRQCANTVA KRTGGTLDIL VNNAGVNAIV PLLDASLDDA KKVYDANVWS VVAMAQAFAP
MLIKAKGTMC NISSVSGEMV FAWAGVYSSS RSAGTRISET LRLELAPLGV RVVTVILGGV
QTSGNDPSNI ADLELPSSSY YQKITAVIDL HKKTMVHPNK QNVDVAAENV VNDLLNGRGI
FIRRGQASTL SWLFNTFLPY RLFTYLINRE SALDKIGFRG DTE
