CITS_MONRU
ID CITS_MONRU Reviewed; 2593 AA.
AC A0A161CEU9; V9I2I1;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 06-JUL-2016, sequence version 1.
DT 03-AUG-2022, entry version 24.
DE RecName: Full=Citrinin polyketide synthase {ECO:0000303|Ref.1};
DE Short=CitS {ECO:0000303|Ref.1};
DE EC=2.3.1.- {ECO:0000269|PubMed:29189834, ECO:0000269|Ref.1};
DE AltName: Full=Non-reducing polyketide synthase citS {ECO:0000303|Ref.1};
GN Name=citS {ECO:0000303|Ref.1}; Synonyms=pksCT {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], FUNCTION, DISRUPTION PHENOTYPE,
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 464-1205.
RC STRAIN=M7;
RA Li L., Chen F.;
RL Submitted (AUG-2010) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INDUCTION.
RC STRAIN=M7;
RX PubMed=27998068; DOI=10.1021/acs.jafc.6b04056;
RA Wang L., Dai Y., Chen W., Shao Y., Chen F.;
RT "Effects of light intensity and color on the biomass, extracellular red
RT pigment, and citrinin production of Monascus ruber.";
RL J. Agric. Food Chem. 64:9506-9514(2016).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, DOMAIN, AND PATHWAY.
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, PubMed:29189834). The pathway begins with the synthesis of
CC a keto-aldehyde intermediate by the citrinin PKS (pksCT also named
CC citS) from successive condensations of 4 malonyl-CoA units, presumably
CC with a simple acetyl-CoA starter unit (Ref.1, PubMed:29189834). Release
CC of the keto-aldehyde intermediate is consistent with the presence of
CC the C-terminal reductive release domain (Ref.1). CitA collaborates with
CC citS by catalyzing the hydrolysis of ACP-bound acyl intermediates to
CC free the ACP from stalled intermediates (PubMed:29189834). CitB then
CC catalyzes the oxidation of the C-12 methyl of the ketone intermediate
CC to an alcohol intermediate which is further oxidized by the
CC oxidoreductase citC to produce a bisaldehyde intermediate (Ref.1). The
CC fourth catalytic step is catalyzed by the citD aldehyde dehydrogenase
CC (Ref.1). The final transformation is the reduction of C-3 by citE to
CC provide the chemically stable citrinin nucleus (Ref.1). CitE appears
CC highly selective for its substrate as its presence in any context other
CC than a full complement of citS and citA-D does not result in observable
CC new compounds (Ref.1). {ECO:0000269|PubMed:29189834,
CC ECO:0000269|Ref.1}.
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000255};
CC Note=Binds 1 phosphopantetheine covalently. {ECO:0000255};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:29189834,
CC ECO:0000269|Ref.1}.
CC -!- INDUCTION: Expression is stimulated under green light conditions
CC (PubMed:27998068). {ECO:0000269|PubMed:27998068}.
CC -!- DOMAIN: Multidomain protein; including an N-terminal starter unit:ACP
CC transacylase (SAT) domain, a beta-ketoacyl synthase (KS) domain, a
CC malonyl-CoA:ACP transacylase (MAT) domain, a product template domain, a
CC acyl carrier protein (ACP) domain, a methyltransferase domain (CMeT)
CC and a reductive NADPH-binding domain that is required for NADPH-
CC dependent product release (Ref.1). The CMet adds methyl groups as
CC check-point tags, which are recognized by KS, such that a lack of
CC methylation causes release of immature products at the triketide stage.
CC {ECO:0000305|PubMed:29189834, ECO:0000305|Ref.1}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of citrinin (Ref.1).
CC {ECO:0000269|Ref.1}.
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DR EMBL; KT781075; ALI92655.1; -; Genomic_DNA.
DR EMBL; HQ123042; AEL33707.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A161CEU9; -.
DR SMR; A0A161CEU9; -.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 2.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR013120; Far_NAD-bd.
DR InterPro; IPR041068; HTH_51.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR013217; Methyltransf_12.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR032088; SAT.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF18558; HTH_51; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF16073; SAT; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..2593
FT /note="Citrinin polyketide synthase"
FT /id="PRO_0000440313"
FT DOMAIN 1661..1738
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 70..224
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000250|UniProtKB:A0A0K0MCJ4"
FT REGION 385..800
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 906..1191
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1322..1601
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1636..1662
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1960..2134
FT /note="Methyltransferase (CMeT) domain"
FT /evidence="ECO:0000255"
FT REGION 2215..2459
FT /note="NADPH-binding (R) domain"
FT /evidence="ECO:0000255"
FT ACT_SITE 139
FT /note="Nucleophile; for transacylase activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0K0MCJ4"
FT ACT_SITE 258
FT /note="Proton donor/acceptor; for transacylase activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0K0MCJ4"
FT ACT_SITE 555
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 1955
FT /note="For methyltransferase activity"
FT /evidence="ECO:0000250|UniProtKB:Q65Z23"
FT ACT_SITE 2067
FT /note="For methyltransferase activity"
FT /evidence="ECO:0000250|UniProtKB:Q65Z23"
FT ACT_SITE 2093
FT /note="For methyltransferase activity"
FT /evidence="ECO:0000250|UniProtKB:Q65Z23"
FT MOD_RES 1698
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2593 AA; 285945 MW; F499D05EF8C37C2C CRC64;
MIDSTSHSNL RSKAFIFGPQ DLSFDVRSFN KLHSQLQNHQ WVLDALASLP KLWDNFAASD
QKVQQSNTGK LLENLNAWIS SGVAPEEAFP LPNVLLSPLV VIGQLVEYMT FLKAAFPDLG
KKHDLPISIK EDTETFGLCT GTLCAFAVAC SSNIADIQHY GAVAARLAML VGAIVDTEEV
LSDPEGKSVS FSASWNSAEF SDSFTHVLET FPDAYVSVIV DQRRATLTAS KKTAPAIIER
LKQEGAHVTS IALSGRFHWK KHQDAVSSLI QFCGLDPDLQ LADATKMLLP SRSSSDGQYI
TTGKLHELAL RAILLEQSEW YKTCRISYLS KFIMDDAAVI CFGPERCMPP TLARKLGPRL
TYVSEIDISS SRVPGQLLGG TQKLNLTDLP DERIAVIGMA CRLPGAEDHE GFWEILKTGQ
SQHREVPEDR FGMATAWREA DKRKWYGNFI DNYDTFDHKF FKKSPREMAS TDPQHRLMLQ
VAYQAVEQSG YFRNNGTNRR IGCFMGVGNV DYEDNIACYP ANAYSATGNL KSFLAGKISH
HFGWTGPSLT LDTACSSSSV AIHQACRSIL SGECNGALAG GVNVITSPNW YHNLAGASFL
SPTGQCKPFD AKGDGYCRGE GVGAVFLKRL SSAIADGDQV FGVIASTKVY QNQNCTAITV
PNAISLSELF TDVVRQARLE PKDITLVEAH GTGTAVGDPA EYDGIRAVFG GPIRSDVLSL
GSVKGLVGHT ECASGVVSLI KTLLMIQQGF IPPQASFSSI NPSLNAKAEE KIEISTRLKP
WDAPFRAALI NNYGASGSNA SMVVTQPPNL TETPSTPLPG KSYPFWISAF DQQSLQSYVR
RLRQFLEKHA ADKNLSVANL SFQVACQSNW SLPQALVFSA STKEELNRAL ASFEKGSTDF
PSVQLPDPKP VILCFGGQVS TYVGLDQEVY NSTAILRHYL DQCDAMCLSL GLQSIYPAIF
QRSPIEDIVQ LQTALFAMQY SCAKAWIDSG LKVASVVGHS FGELIALCVS NAVSLKDAVK
MISGRARLIK ERWGADKGSM IAVEADLSDV EALLAKVKSQ MGSETGLAIA CYNASKSFTL
AGPTKDVDHA ENLLKNDPDF SGIRYKRLNV TNAFHSVLVD ALIDDLESLG QGIRFKEPTI
KLERATEQES TSTLNANYVA THMRKPVFFA QAVKRLSDKF PVAIWLEAGS NSTITAMASR
ALGTSNSSFQ AVNITSEGAF RFLCDTTVKL WKEGQKVSFW AHHRLQTPMY TPVLLPPYQF
EKSRHWMDLK VPPKPEASVQ VAEQTAIIEA PKGLTTFVGY QDASQRSVRF RVNVTTEKFN
RLLSGHIMAN AAAVCPGMFQ VEIALDALTS LRPEFQARSF IPELHDLRHY QPLVRDESRA
VWIEAHCPNA EGLVWNWKLT ASDDKGSGSV THTSGTITFQ AADSVQVKSE FEKLRRLIGR
KRCLQLLDSN VADDILQGRN IYRAFTEVID YKEIYRHVTK IAGRDNESAG RVIKTYDGET
WLDTVLTDCF CQVAGIFVNL MTTKIDLSER GIFICDGIDR WLRAPNAGSN NTPSQVYEVF
ALHHCESDSK YLSDVFAFDA REGSLVEVAL GISYQKVSIS GIRRVLSKGM PAGLQPQVPT
SPAAVAAIKT VSPPPVADSP LVDGSSTAVS GTPPTKKAPK APSVDITGKM REIICNLSGL
EPDEVKDDSD LVELGIDSLM SMELAREVDL AFKTTIDVTQ LIDVTDFRSL VECMQRILGI
DNQEDNTYLA EGLNGHEGVV TNGNAYHVNG TNGVVNGNGV LFPELGGSIL PKSAILDAFR
IAKEATDDFI LNGQLGTYYN EVMPRSTELC VAHIVNAFEQ LGCPIRSAAA YQRLERVPYL
PKHERFMNLI YGLLEEARLI DINGSEITRT SVPVSTKSVE TMLEELLHDE PLHAAEHKLT
SLTGSKFADC ITGKEDGLQL IFGSPEGREI VTDVYAKSPI NAVWIQQAEF FLEQLVKRLP
NTGEPLRILE MGAGTGGTTV KMLPLLERLG VPVEYTMTDL SSSLIAAARK RFKKYPFMKF
KVVNIESPPD PQLVHSQHII LATNCVHATR NLEISTRNIH RILRPDGFLL LLEMTEQVPW
VDFIFGLLEG WWLFEDGRRH ALQPATHWKK ILTSVGYGHV DWTEGTRPEA NIQRLIIALA
SEPRYDHTPQ SLQPPVQVPL TDIAGRQEII DTYIREYTED FRALPIPGIQ QAVMPAPTGH
CVLVTGATGS LGSHVVGYLS RLPNVHTVVC LNRRSTVPAT IRQEEALKVR GISLDDNSRS
KLVVLEVETA KPLLGLPVET YQKLVNTATH IVHSAWPMSL TRPIRGYESQ FKVMQNLINL
AREVAAWRPV PFKFSFQFIS SIGVVGYYPL RYGEIIAPEE TMTADSVLPV GYAEAKLVCE
RMLDETLHQY PDRFRPMAVR IAQIAGSTSN GHWNPVEHFA FLIKSSQTLK ALPDFDGSLS
WCPVDDVSAT LGELLISNTT PYSIYHIENP SRQQWRKMVK TLAQSLDIPR DGIIPFDQWI
ERVRNSSASI NDNPARQLLE FFDQHFIRMS CGNLILDTTK TREHSATLRE RGPVGPGLVE
KYISAWKTMG FLD
