ID TROPA_TALSN Reviewed; 2661 AA.
AC B8M9J9;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 27-MAR-2024, entry version 87.
DE RecName: Full=3-methylorcinaldehyde synthase tropA {ECO:0000303|PubMed:22508998};
DE Short=MOS {ECO:0000303|PubMed:22508998};
DE EC=2.3.1.- {ECO:0000269|PubMed:22508998};
DE AltName: Full=Non-reducing polyketide synthase tropA {ECO:0000303|PubMed:22508998};
DE AltName: Full=Tropolone synthesis protein A {ECO:0000303|PubMed:22508998};
GN Name=tropA {ECO:0000303|PubMed:22508998};
GN Synonyms=tspks1 {ECO:0000303|PubMed:22508998}; ORFNames=TSTA_117750;
OS Talaromyces stipitatus (strain ATCC 10500 / CBS 375.48 / QM 6759 / NRRL
OS 1006) (Penicillium stipitatum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Trichocomaceae; Talaromyces;
OC Talaromyces sect. Talaromyces.
OX NCBI_TaxID=441959;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP CATALYTIC ACTIVITY.
RC STRAIN=ATCC 10500 / CBS 375.48 / QM 6759 / NRRL 1006;
RX PubMed=22508998; DOI=10.1073/pnas.1201469109;
RA Davison J., al Fahad A., Cai M., Song Z., Yehia S.Y., Lazarus C.M.,
RA Bailey A.M., Simpson T.J., Cox R.J.;
RT "Genetic, molecular, and biochemical basis of fungal tropolone
RT biosynthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:7642-7647(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 10500 / CBS 375.48 / QM 6759 / NRRL 1006;
RX PubMed=24863423; DOI=10.1002/anie.201403450;
RA al Fahad A., Abood A., Simpson T.J., Cox R.J.;
RT "The biosynthesis and catabolism of the maleic anhydride moiety of
RT stipitatonic acid.";
RL Angew. Chem. Int. Ed. 53:7519-7523(2014).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 10500 / CBS 375.48 / QM 6759 / NRRL 1006;
RX PubMed=25676766; DOI=10.1128/genomea.01559-14;
RA Nierman W.C., Fedorova-Abrams N.D., Andrianopoulos A.;
RT "Genome sequence of the AIDS-associated pathogen Penicillium marneffei
RT (ATCC18224) and its near taxonomic relative Talaromyces stipitatus
RT (ATCC10500).";
RL Genome Announc. 3:E0155914-E0155914(2015).
CC -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of the tropolone class of fungal maleic
CC anhydrides (PubMed:22508998, PubMed:24863423). The pathway begins with
CC the synthesis of 3-methylorcinaldehyde by the non-reducing polyketide
CC synthase (PKS) tropA (PubMed:22508998). 3-methylorcinaldehyde is the
CC substrate for the FAD-dependent monooxygenase tropB to yield a
CC dearomatized hydroxycyclohexadione (PubMed:22508998, PubMed:24863423).
CC The 2-oxoglutarate-dependent dioxygenase tropC then performs the
CC oxidative ring expansion to provide the first tropolone metabolite
CC stipitaldehyde (PubMed:22508998, PubMed:24863423). Trop D converts
CC stipitaldehyde into stipitacetal which is in turn converted to
CC stipitalide by the short-chain dehydrogenase/reductase tropE
CC (PubMed:24863423). The next steps involve tropF, tropG, tropH, tropI
CC and tropJ to form successive tropolone maleic anhydrides including
CC stipitaldehydic, stipitatonic and stipitatic acids (PubMed:24863423).
CC {ECO:0000269|PubMed:22508998, ECO:0000269|PubMed:24863423}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:22508998}.
CC -!- DOMAIN: Multidomain protein; including a starter unit:ACP transacylase
CC (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes
CC repeated decarboxylative condensation to elongate the polyketide
CC backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and
CC transfers the extender unit malonyl-CoA; a product template (PT) domain
CC that controls the immediate cyclization regioselectivity of the
CC reactive polyketide backbone; and an acyl-carrier protein (ACP) that
CC serves as the tether of the growing and completed polyketide via its
CC phosphopantetheinyl arm. {ECO:0000305}.
CC -!- DOMAIN: The release of the polyketide chain from the non-reducing
CC polyketide synthase is mediated by the thioesterase (TE) domain
CC localized at the C-ter of the protein. {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of tropolones
CC (PubMed:22508998). {ECO:0000269|PubMed:22508998}.
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DR EMBL; BK008910; DAA64703.1; -; Genomic_DNA.
DR EMBL; EQ962655; EED18001.1; -; Genomic_DNA.
DR RefSeq; XP_002481993.1; XM_002481948.1.
DR AlphaFoldDB; B8M9J9; -.
DR SMR; B8M9J9; -.
DR STRING; 441959.B8M9J9; -.
DR GeneID; 8105833; -.
DR VEuPathDB; FungiDB:TSTA_117750; -.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_6_2_1; -.
DR InParanoid; B8M9J9; -.
DR OrthoDB; 5396558at2759; -.
DR PhylomeDB; B8M9J9; -.
DR BioCyc; MetaCyc:MONOMER-19386; -.
DR Proteomes; UP000001745; Unassembled WGS sequence.
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:0018130; P:heterocycle biosynthetic process; IEA:UniProt.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:1901362; P:organic cyclic compound biosynthetic process; IEA:UniProt.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR CDD; cd02440; AdoMet_MTases; 1.
DR CDD; cd00833; PKS; 1.
DR Gene3D; 3.30.70.3290; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 1.10.1200.10; ACP-like; 2.
DR Gene3D; 3.40.366.10; Malonyl-Coenzyme A Acyl Carrier Protein, domain 2; 2.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR Gene3D; 3.10.129.110; Polyketide synthase dehydratase; 1.
DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 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; 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 PANTHER; PTHR45681:SF6; CARRIER DOMAIN-CONTAINING PROTEIN; 1.
DR PANTHER; PTHR45681; POLYKETIDE SYNTHASE 44-RELATED; 1.
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; 2.
DR Pfam; PF16073; SAT; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 2.
DR SMART; SM01294; PKS_PP_betabranch; 1.
DR SUPFAM; SSF47336; ACP-like; 2.
DR SUPFAM; SSF52151; FabD/lysophospholipase-like; 1.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR SUPFAM; SSF55048; Probable ACP-binding domain of malonyl-CoA ACP transacylase; 1.
DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR SUPFAM; SSF53901; Thiolase-like; 1.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00606; KS3_1; 1.
DR PROSITE; PS52004; KS3_2; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
DR PROSITE; PS52019; PKS_MFAS_DH; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat;
KW Transferase.
FT CHAIN 1..2661
FT /note="3-methylorcinaldehyde synthase tropA"
FT /id="PRO_0000437127"
FT DOMAIN 380..796
FT /note="Ketosynthase family 3 (KS3)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT DOMAIN 1283..1600
FT /note="PKS/mFAS DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT DOMAIN 1654..1731
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1764..1841
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 14..271
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255"
FT REGION 901..1211
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1283..1425
FT /note="N-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1288..1599
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1453..1600
FT /note="C-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1614..1656
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1734..1762
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1998..2231
FT /note="Methyltransferase (CMeT) domain"
FT /evidence="ECO:0000255"
FT REGION 2271..2659
FT /note="Thioesterase (TE) domain"
FT /evidence="ECO:0000250|UniProtKB:Q5ATJ7"
FT COMPBIAS 1614..1640
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 545
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 680
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 719
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 988
FT /note="For acyl/malonyl transferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 1318
FT /note="Proton acceptor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT ACT_SITE 1509
FT /note="Proton donor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT MOD_RES 1691
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1801
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2661 AA; 293856 MW; 96FE428D021E6E7E CRC64;
MDPLASNFRG ETVLLFGSQS LSFDANTFNA IRSSLEKEEY LRWIRHTVAD LPSALNTALQ
HVPHLKGSEE WAFSAVQELN DWLDSGHQPN SLDPSALPNT ILTPLVVILH LSQYMKYLIS
ANDYQDDTLL SKRQQETCET LGLCTGLLSS LAVSSSRTRL QLERYGSVAI RLAMLIGLIV
DARDRSTSHG PSQSTAALWH SEEQKEKLLE ILAANPEAYI SVYYDQNRAT ITIPTAQTAT
IRKDLASAGL TTTEIGLRGR FHWSGHEAEV DQLIKLCDID KRFQFTQKTA LVLPNRSFDS
EPHVHQGPLH AMALWSILVN PPEWQKTVSA VYASTLVSTT AKVVSFGQER CVPPTILQNL
DSRVFYMGDL EKTSSPRPRG DDIAIVGASI KVAGADDLEE FWEILSKGIS QHKEVPPERF
TFDTVYRDRD PKTKWYGNFL NDPDKFDHKF FKKSPREAES MDPQQRLLLQ IAYQALEKGG
YFHNAGPDQR IGCYMGVCAV DYENNLACYA PNAFTATSHL RGFIAGKVSH YFGWTGPALT
IDTACSSSAV AVHLACQAIL KGECTAALAG GTQILTSPLW FQNLAGASFL SKTGQCKPFD
SKADGYCRGE AVGAVFLKKM SAALADGDQI LGVISGTAVQ QNENCTPIVV PNKPSLSDMF
QSVIEKARLQ PDHITVVEAH GTGTAVGDPV EYASVRDTLG GSKRTKKLFL GSAKGLVGHC
ESASGIISLV KVLLMIQKGM IPPQASFNTL NPATKATPAD GIEISRQLTE WNAPFRAALI
NNYGASGSNA SMVITQAPRA TTTIPGGNEM ERVPFWFSAL NEKSLQAYAA EFLKYLKANH
GQLSLPDLGF NVSRQSNRSL PRRLLFTCQS TNELQQRLEE YVKGDSKTSS SECPATRPLV
LCFGGQVSTF IGLSRQVYED VALLRGHLNS CNRRCLALGL RGIFPAIFQK GPIEDIVTLQ
LSLFAMQYSC AKSWIDAGAQ PVAVLGHSFG ELTALCVSGV LSLDDALRMI AARAQIIRDS
WGSDGGSMMA LEADLDVVQK LLATSNANLP ENEVAVIACY NGPRSFTIAG PRRAIDALDT
SRQASPEFAS IKAKRLDVTN AFHSTLVEPL RNKLTEATKE LNFRERGTIH LERSTETRSE
KLIDNPGSYV ADHMRNPVFF HHALQRLDNQ FPNAIYLEAG SSSTITNMAS RALGGSGGRH
FQAMSITTDK GLDNLIDATM SLWNAGLNVR FWKQAFVETE NYKPLLLPPY QFEKSRHWLE
LKEPPKPEII TMSAGGQRTD KAPDTILSFV GYQDSNKSHA RFRLNTENRE YQELMKAHLI
VYTAPICPAT VQMDIAIEGL KTLVPGIGSE VQPQIHNVDN QTPICADKSQ SIWLDMKLAD
EPSKISWRFR FFGTSLDNDK MPSNKQADAG VTFTLGTLVV VPMEDEQTKL DLTRYDLLTG
HKRCVELLHS TEAEEILQGR TIYKTFADIV DYGEQYRGLQ RLIGHGNNSV GRVVRAYNPK
TWFDAHLSDA YAQVVGIWLN CMTEHDAEEL YVARGFEKWI RSPDIQPTSR PDSYDVLAYH
KGPSRNSCLS DIFVFHPKTG QLIEAILGFQ FVRIPRKGLA KLLTRLTRDE TALATNAQSR
AIPPPSTNTT QSSSQQTPIP KAAAPKKEKK RPGNPKLDVL PKLITILADL VGLEPEEITI
NSELADIGVD SLMAMEVVTE IERVFSCSVP LDDVADVTTM SQLVRVVESI VGMEGSETSN
LSSDDDDENG TPSTPETDLS DASVDAVVDN AELIAYFAES LGMDASEISA NVQLKELGVD
SLLSMELGGE LVEKFGLNLN ESTVLEDMTI NDLRQTAPGA AAPKVAESTI TSAPQVTTSK
AVPLTNGTSF NIPVETILSA FKETKAAGDS FITATGCRGY VEQVLPEQTL LCALHTLEAF
EKMGSSIRTL KAGDTMTLFT PRPEYVSLIE RLTEMLETQI GLIKVIGGPG LTIERTQTPY
PTASSTVLMQ EMRQKYPQYQ NVNELIFYVG SNLDRALRGE TDGIKLIFGC AQGRELVSGL
YGDWIMNICY YRQMEDFLIR LIAKLPSNEP LRILEMGAGT GGTSKWLLPL LARLGCPVEY
TFTDLAPSLV AGARKTFKQY ASFMKFRAHD IEQEPAEDLL GTQHMVVASN AVHATVSLVE
SAKKLRKVLR PNGILMMLEM IEPLYWIDMI FGLFEGWWLF ADGRKHALTP PARWKTDLQA
AGFGRVDWSD GNLPENSINK VIIAVACEPE KPEELDRKSV VDEFVHKYTQ GVDLLSPAIR
VNRKSLGHAV LVTGGTGSVG AHVVAHLAQQ PFVTKVICLN RRGKLDARQR QLESLAQKGL
QLSDESLAKI QVYETDLSKP QLGLSPEMYL SLLESTTDII HNAWPMSIKR QVQGFEAQFR
IMRNLIEFAR DISLGGGDPL GFQFISSIAT VGHYPLWKQE IRVPEDRLPL DAVLPIGYGD
AKYICELMLD KTLHTYPHRF RVSTVRLGQV GGSKISGYWN PVEHLSFLFK SAQTIQQLPD
LHGPLSWTPV DDVAKSLVDL LFTEKPYPVY HIENPITQPW QEMIPILADA LGIPRGNRLS
LKDWVARVRE FPEDPTDKDK NPATALVDFF EQDFERMSVG GLLLDTTKSR EHSPSLRAVG
PITPDLVRKF ISYWRSISFV A
//
