CCTM_TALIS
ID CCTM_TALIS Reviewed; 395 AA.
AC A0A0U1LQD9;
DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT 17-FEB-2016, sequence version 1.
DT 03-AUG-2022, entry version 20.
DE RecName: Full=FAD-dependent monooxygenase cctM {ECO:0000303|PubMed:26954535};
DE EC=1.-.-.- {ECO:0000305|PubMed:26954535};
DE AltName: Full=Cyclochlorotine biosynthesis protein M {ECO:0000303|PubMed:26954535};
DE Flags: Precursor;
GN Name=cctM {ECO:0000303|PubMed:26954535}; ORFNames=PISL3812_02618;
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: FAD-dependent monooxygenase; 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 -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:26954535}.
CC -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; CVMT01000002; CRG85571.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A0U1LQD9; -.
DR SMR; A0A0U1LQD9; -.
DR EnsemblFungi; CRG85571; CRG85571; PISL3812_02618.
DR OMA; HPMTFHR; -.
DR OrthoDB; 817726at2759; -.
DR Proteomes; UP000054383; Unassembled WGS sequence.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 2.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 3: Inferred from homology;
KW FAD; Flavoprotein; Glycoprotein; Monooxygenase; Oxidoreductase;
KW Reference proteome; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..395
FT /note="FAD-dependent monooxygenase cctM"
FT /id="PRO_0000438666"
FT BINDING 38..39
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 306
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 316..320
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 298
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 395 AA; 43436 MW; 55E96494B949256E CRC64;
MEPGTDVRRV LVIGAGAAGL LIAQVLKKHG VPCTVFEQDT KADARPRDWN YGIYWAQSYL
AECLPPELVS QLESAQVDSH TPSGSDILPT FNLATGEPLI SVSAPYSYRL QRRKFLNLIS
TGIDIQYGKR LTMVDSDNKT VTAVFEDSSQ ATGNLLIGTE GAHSRVREYL LGKERAAVIP
SRIVASATVS RLPEREVSAL RKLHPRYCIA IHPDGYFNWL GIHDEAAQSK DCTFMIILSW
ISESDTGLSG TAIAADLKER ANTFGEPFRT VLQSIPSETT FWHNRLSSWP TQPWNSHNGT
VTLAGDAAHP MTFHRGQGLN NAITDAAYFG RQLAALDTKS TESLSAVVTA FEEELWKRGN
EAVTQSDINS LSVHNWEELK SSPLFTSGLK QRSST
