ID   CITD_MONRU              Reviewed;         501 AA.
AC   A0A162J448;
DT   07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT   06-JUL-2016, sequence version 1.
DT   03-AUG-2022, entry version 18.
DE   RecName: Full=Aldehyde dehydrogenase citD {ECO:0000303|Ref.1};
DE            EC=1.2.1.3 {ECO:0000255|PROSITE-ProRule:PRU10007};
DE   AltName: Full=Citrinin synthesis protein D {ECO:0000303|Ref.1};
GN   Name=citD {ECO:0000303|Ref.1}; Synonyms=mrl4 {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   -!- CATALYTIC ACTIVITY:
CC       Reaction=an aldehyde + H2O + NAD(+) = a carboxylate + 2 H(+) + NADH;
CC         Xref=Rhea:RHEA:16185, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17478, ChEBI:CHEBI:29067, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945; EC=1.2.1.3; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU10007};
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|Ref.1}.
CC   -!- DISRUPTION PHENOTYPE: Leads to complete absence of citrinin production
CC       (Ref.1). {ECO:0000269|Ref.1}.
CC   -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC       {ECO:0000255}.
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DR   EMBL; KT781075; ALI92651.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A162J448; -.
DR   SMR; A0A162J448; -.
DR   GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; IEA:UniProtKB-EC.
DR   GO; GO:0043878; F:glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity; IEA:UniProtKB-EC.
DR   Gene3D; 3.40.309.10; -; 1.
DR   Gene3D; 3.40.605.10; -; 1.
DR   InterPro; IPR016161; Ald_DH/histidinol_DH.
DR   InterPro; IPR016163; Ald_DH_C.
DR   InterPro; IPR016160; Ald_DH_CS_CYS.
DR   InterPro; IPR029510; Ald_DH_CS_GLU.
DR   InterPro; IPR016162; Ald_DH_N.
DR   InterPro; IPR015590; Aldehyde_DH_dom.
DR   Pfam; PF00171; Aldedh; 1.
DR   SUPFAM; SSF53720; SSF53720; 1.
DR   PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1.
DR   PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1.
PE   1: Evidence at protein level;
KW   NAD; Oxidoreductase.
FT   CHAIN           1..501
FT                   /note="Aldehyde dehydrogenase citD"
FT                   /id="PRO_0000440321"
FT   ACT_SITE        253
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10007"
FT   ACT_SITE        287
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10008"
FT   BINDING         231..236
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q28399"
SQ   SEQUENCE   501 AA;  54135 MW;  294E2D92F88C25F0 CRC64;
     MAEAAARILE ALPAVCEYRW SCKDASKRFT VVNPATGEPI TVVQAGNLDT VQGAIQASHR
     AFESWRWKTR QERSLYLLQA ADELQKHSHE LAVLLCLENG KPVKDASFDV GFLVQVFRYF
     GSIVDKLPSE FFDQGSIYSS VIYEPHGVCV GILPFNWPPV HAGGKLAPCL AAGNTMVLKP
     GEQAPLTLMR IVEILQSVFP ADVVQAVPGL GPEIPQALIN HPLVKMVSLT GSTASGSQAA
     QTAAVTLTPT VLELGGKNAF VVFEDADLEL VVRDAIDGAF FNKGESCTAA SRILVHKDLY
     PTLVSRLTAA VKKLRTGDGL DETTHIGPVV SRERQQEVLS YIEQGKREGA TLAAQGDPPT
     AGRLSGGFFV PPTLFTDVTA DMTIAQREIF GPVVTVGSFE TEEEAVKTVN SSQYGLFAGV
     YSSDFTRAMR VTRKLDVGVV LVNNYFRALL GTPFGGVKDS GYGREHWIGT LREWSRVKNV
     RFPSGLSPIP AWGGAVDVCK L