CITC_MONRU
ID CITC_MONRU Reviewed; 622 AA.
AC A0A161CEV4;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 06-JUL-2016, sequence version 1.
DT 03-AUG-2022, entry version 17.
DE RecName: Full=Dehydrogenase citC {ECO:0000303|Ref.1};
DE EC=1.1.-.- {ECO:0000305|Ref.1};
DE AltName: Full=Citrinin synthesis protein C {ECO:0000303|Ref.1};
GN Name=citC {ECO:0000303|Ref.1}; Synonyms=mrl7 {ECO:0000303|Ref.1};
OS Monascus ruber (Mold).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Monascus.
OX NCBI_TaxID=89489;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], DISRUPTION PHENOTYPE, FUNCTION,
RP CATALYTIC ACTIVITY, AND PATHWAY.
RC STRAIN=M7;
RX DOI=10.1039/C5SC04027B;
RA He Y., Cox R.J.;
RT "The molecular steps of citrinin biosynthesis in fungi.";
RL Chem. Sci. 7:2119-2127(2016).
RN [2]
RP FUNCTION.
RX PubMed=29189834; DOI=10.1039/c7cc07079a;
RA Storm P.A., Townsend C.A.;
RT "In trans hydrolysis of carrier protein-bound acyl intermediates by CitA
RT during citrinin biosynthesis.";
RL Chem. Commun. (Camb.) 54:50-53(2017).
CC -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of the mycotoxin citrinin, a hepato-
CC nephrotoxic compound to humans due to inhibition of respiration complex
CC III (Ref.1). The pathway begins with the synthesis of a keto-aldehyde
CC intermediate by the citrinin PKS (pksCT also named citS) from
CC successive condensations of 4 malonyl-CoA units, presumably with a
CC simple acetyl-CoA starter unit (Ref.1). Release of the keto-aldehyde
CC intermediate is consistent with the presence of the C-terminal
CC reductive release domain (Ref.1). CitA collaborates with citS by
CC catalyzing the hydrolysis of ACP-bound acyl intermediates to free the
CC ACP from stalled intermediates (PubMed:29189834). CitB then catalyzes
CC the oxidation of the C-12 methyl of the ketone intermediate to an
CC alcohol intermediate which is further oxidized by the oxidoreductase
CC citC to produce a bisaldehyde intermediate (Ref.1). The fourth
CC catalytic step is catalyzed by the citD aldehyde dehydrogenase (Ref.1).
CC The final transformation is the reduction of C-3 by citE to provide the
CC chemically stable citrinin nucleus (Ref.1). CitE appears highly
CC selective for its substrate as its presence in any context other than a
CC full complement of citS and citA-D does not result in observable new
CC compounds (Ref.1). {ECO:0000269|PubMed:29189834, ECO:0000269|Ref.1}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:E4QP00};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|Ref.1}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q12062}.
CC -!- DISRUPTION PHENOTYPE: Leads to complete absence of citrinin production
CC (Ref.1). {ECO:0000269|Ref.1}.
CC -!- SIMILARITY: Belongs to the GMC oxidoreductase family. {ECO:0000305}.
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DR EMBL; KT781075; ALI92648.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A161CEV4; -.
DR SMR; A0A161CEV4; -.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0016614; F:oxidoreductase activity, acting on CH-OH group of donors; IEA:InterPro.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR012132; GMC_OxRdtase.
DR InterPro; IPR000172; GMC_OxRdtase_N.
DR InterPro; IPR007867; GMC_OxRtase_C.
DR PANTHER; PTHR11552; PTHR11552; 1.
DR Pfam; PF05199; GMC_oxred_C; 1.
DR Pfam; PF00732; GMC_oxred_N; 1.
DR PIRSF; PIRSF000137; Alcohol_oxidase; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR PROSITE; PS00623; GMC_OXRED_1; 1.
DR PROSITE; PS00624; GMC_OXRED_2; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Oxidoreductase.
FT CHAIN 1..622
FT /note="Dehydrogenase citC"
FT /id="PRO_0000440319"
FT ACT_SITE 554
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 23..24
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 44..45
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 102..105
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 582
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 593..594
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
SQ SEQUENCE 622 AA; 66811 MW; DA62628BF2519E33 CRC64;
MATVKVIDFI QTPFDFLIVG GGTAGLVLAA RLSEEPGIQV GVIEAGSLRL GDPKVDLPTG
PGQMLGDPGY DWNFESIPQA GANAKAYHIP RGRMLGGSSG INFMSYNRPS AEDIDDWANK
LGVKGWTWSE LLPYFKRSEN LEPIEPSASC PVSPKVHGTG GPIHTSIGPW QAPIEESLLA
AFDEAARLQR PAEPYSGAHL GFYRSLFTLD RTSTPVRSYA VSGYYAPVMG RPNLKVLENA
QVCRILLSDA SDGIPVAEGV ELHHAGARYA VSARREVILS AGSVQSPQLL ELSGIGDPSV
LEGAGIACRV ANTDVGSNLQ EHTMSAVSYE CADGIMSVDS LFKDPALLEE HQSLYAKNHS
GALSGSVSLM GFTPYSSLST ETQVDATMAR IFDAPSVSGR LSQQNASYQR RQQEAVAARM
QNRWSADIQF IGTPAYFNTA AGYASCAKIM SGPPVGYSAC YSIVVSNMYP LSRGSVHVRT
SNPMDAPAID PGFLSHPVDV DVLAAGIVFA DRVFRSTLLN GKVRRRVSPP AGLDLSNMDE
ARQFVRNHIV PYHHALGTCA MGQVVDEKLR VKGVRRLRVV DASVMPMQVS AAIMATVYAI
AERASDIIKK DCGFGRRLRA HI
