CITS_MONPU
ID CITS_MONPU Reviewed; 2593 AA.
AC Q65Z23;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2017, sequence version 2.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Citrinin polyketide synthase {ECO:0000303|PubMed:16000748};
DE EC=2.3.1.- {ECO:0000269|PubMed:27913218, ECO:0000269|PubMed:28238725};
DE AltName: Full=Non-reducing polyketide synthase citS {ECO:0000303|PubMed:16000748};
GN Name=pksCT {ECO:0000303|PubMed:16000748};
OS Monascus purpureus (Red mold) (Monascus anka).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Monascus.
OX NCBI_TaxID=5098;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=16000748; DOI=10.1128/aem.71.7.3453-3457.2005;
RA Shimizu T., Kinoshita H., Ishihara S., Sakai K., Nagai S., Nihira T.;
RT "Polyketide synthase gene responsible for citrinin biosynthesis in Monascus
RT purpureus.";
RL Appl. Environ. Microbiol. 71:3453-3457(2005).
RN [2]
RP FUNCTION.
RX PubMed=19012408; DOI=10.1021/jf802371b;
RA Chen Y.P., Tseng C.P., Chien I.L., Wang W.Y., Liaw L.L., Yuan G.F.;
RT "Exploring the distribution of citrinin biosynthesis related genes among
RT Monascus species.";
RL J. Agric. Food Chem. 56:11767-11772(2008).
RN [3]
RP FUNCTION.
RX PubMed=19111642; DOI=10.1263/jbb.106.466;
RA Sakai K., Kinoshita H., Shimizu T., Nihira T.;
RT "Construction of a citrinin gene cluster expression system in heterologous
RT Aspergillus oryzae.";
RL J. Biosci. Bioeng. 106:466-472(2008).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=27913218; DOI=10.1016/j.jbiotec.2016.11.031;
RA Xue Y., Kong C., Shen W., Bai C., Ren Y., Zhou X., Zhang Y., Cai M.;
RT "Methylotrophic yeast Pichia pastoris as a chassis organism for polyketide
RT synthesis via the full citrinin biosynthetic pathway.";
RL J. Biotechnol. 242:64-72(2017).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 1785-2163 IN COMPLEX WITH
RP COSUBSTRATE, GENE MODEL REVISION, DOMAIN, FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVE SITE, AND MUTAGENESIS OF TYR-1955 AND HIS-2067.
RX PubMed=28238725; DOI=10.1016/j.chembiol.2017.01.008;
RA Storm P.A., Herbst D.A., Maier T., Townsend C.A.;
RT "Functional and structural analysis of programmed C-methylation in the
RT biosynthesis of the fungal polyketide citrinin.";
RL Cell Chem. Biol. 24:316-325(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 (PubMed:16000748, PubMed:19012408, PubMed:19111642,
CC PubMed:27913218, PubMed:28238725). The pathway begins with the
CC synthesis of a keto-aldehyde intermediate by the citrinin PKS (pksCT)
CC from successive condensations of 4 malonyl-CoA units, presumably with a
CC simple acetyl-CoA starter unit (PubMed:28238725). Release of the keto-
CC aldehyde intermediate is consistent with the presence of the C-terminal
CC reductive release domain (PubMed:28238725). Mp11 collaborates with
CC pksCT by catalyzing the hydrolysis of ACP-bound acyl intermediates to
CC free the ACP from stalled intermediates (By similarity). Mpl2 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 mpl7 to produce a bisaldehyde intermediate
CC (PubMed:27913218). The fourth catalytic step is catalyzed by the mpl4
CC aldehyde dehydrogenase (PubMed:27913218). The final transformation is
CC the reduction of C-3 by mpl6 to provide the chemically stable citrinin
CC nucleus (PubMed:27913218). {ECO:0000250|UniProtKB:A0A161CKG1,
CC ECO:0000269|PubMed:16000748, ECO:0000269|PubMed:19012408,
CC ECO:0000269|PubMed:19111642, ECO:0000269|PubMed:27913218,
CC ECO:0000269|PubMed:28238725}.
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:16000748,
CC ECO:0000269|PubMed:28238725}.
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 (PubMed:16000748, PubMed:28238725). The CMet
CC adds methyl groups as check-point tags, which are recognized by KS,
CC such that a lack of methylation causes release of immature products at
CC the triketide stage (PubMed:28238725). {ECO:0000305|PubMed:16000748,
CC ECO:0000305|PubMed:28238725}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of citrinin
CC (PubMed:16000748). {ECO:0000269|PubMed:16000748}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD44749.1; Type=Erroneous gene model prediction; Evidence={ECO:0000269|PubMed:28238725};
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DR EMBL; AB167465; BAD44749.1; ALT_SEQ; Genomic_DNA.
DR PDB; 5MPT; X-ray; 1.65 A; A=1785-2163.
DR PDBsum; 5MPT; -.
DR AlphaFoldDB; Q65Z23; -.
DR SMR; Q65Z23; -.
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 3D-structure; Acyltransferase; Methyltransferase; Multifunctional enzyme;
KW NADP; Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..2593
FT /note="Citrinin polyketide synthase"
FT /id="PRO_0000440312"
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:0000269|PubMed:28238725"
FT ACT_SITE 2067
FT /note="For methyltransferase activity"
FT /evidence="ECO:0000269|PubMed:28238725"
FT ACT_SITE 2093
FT /note="For methyltransferase activity"
FT /evidence="ECO:0000269|PubMed:28238725"
FT MOD_RES 1689
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MUTAGEN 1955
FT /note="Y->A,F: Affects the production of tetra- and
FT pentaketide chains."
FT /evidence="ECO:0000269|PubMed:28238725"
FT MUTAGEN 2067
FT /note="H->A: Blocks the elongation of the polyketide
FT backbone at the triketide step, matching the profile of the
FT minimal PKS without the CMeT domain."
FT /evidence="ECO:0000269|PubMed:28238725"
FT MUTAGEN 2067
FT /note="H->A: Leads to the accumulation of a major triketide
FT product in addition to smaller amounts of two different
FT other triketides identical by mass, but singly methylated
FT at C-4 and C-2, respectively."
FT /evidence="ECO:0000269|PubMed:28238725"
FT HELIX 1792..1804
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 1806..1812
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 1818..1821
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 1823..1840
FT /evidence="ECO:0007829|PDB:5MPT"
FT TURN 1845..1847
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 1861..1863
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 1864..1876
FT /evidence="ECO:0007829|PDB:5MPT"
FT STRAND 1879..1883
FT /evidence="ECO:0007829|PDB:5MPT"
FT STRAND 1886..1889
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 1899..1909
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 1911..1913
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 1914..1924
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 1927..1931
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 1937..1942
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 1945..1956
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 1959..1976
FT /evidence="ECO:0007829|PDB:5MPT"
FT STRAND 1986..1992
FT /evidence="ECO:0007829|PDB:5MPT"
FT TURN 1994..1998
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 1999..2009
FT /evidence="ECO:0007829|PDB:5MPT"
FT STRAND 2013..2020
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 2022..2031
FT /evidence="ECO:0007829|PDB:5MPT"
FT TURN 2032..2034
FT /evidence="ECO:0007829|PDB:5MPT"
FT STRAND 2038..2042
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 2051..2053
FT /evidence="ECO:0007829|PDB:5MPT"
FT STRAND 2057..2064
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 2066..2068
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 2072..2082
FT /evidence="ECO:0007829|PDB:5MPT"
FT STRAND 2083..2094
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 2099..2105
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 2109..2111
FT /evidence="ECO:0007829|PDB:5MPT"
FT STRAND 2119..2121
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 2125..2134
FT /evidence="ECO:0007829|PDB:5MPT"
FT STRAND 2139..2142
FT /evidence="ECO:0007829|PDB:5MPT"
FT HELIX 2148..2151
FT /evidence="ECO:0007829|PDB:5MPT"
FT STRAND 2153..2161
FT /evidence="ECO:0007829|PDB:5MPT"
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
