TDIA_EMENI
ID TDIA_EMENI Reviewed; 970 AA.
AC A7XRY0; C8VEN2; Q5AT67;
DT 08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Didemethylasterriquinone D synthetase tdiA {ECO:0000303|PubMed:17704773};
DE EC=2.3.1.- {ECO:0000269|PubMed:17704773};
DE AltName: Full=Nonribosomal peptide synthase tdiA {ECO:0000305};
DE AltName: Full=Terrequinone biosynthesis protein A {ECO:0000303|PubMed:16426969};
GN Name=tdiA {ECO:0000303|PubMed:16426969}; ORFNames=AN8513;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF SER-774.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=17704773; DOI=10.1038/nchembio.2007.20;
RA Balibar C.J., Howard-Jones A.R., Walsh C.T.;
RT "Terrequinone A biosynthesis through L-tryptophan oxidation, dimerization
RT and bisprenylation.";
RL Nat. Chem. Biol. 3:584-592(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
RN [4]
RP IDENTIFICATION, AND INDUCTION.
RX PubMed=16426969; DOI=10.1016/j.chembiol.2005.10.008;
RA Bok J.W., Hoffmeister D., Maggio-Hall L.A., Murillo R., Glasner J.D.,
RA Keller N.P.;
RT "Genomic mining for Aspergillus natural products.";
RL Chem. Biol. 13:31-37(2006).
RN [5]
RP IDENTIFICATION, INDUCTION, AND FUNCTION.
RX PubMed=17291795; DOI=10.1016/j.fgb.2006.12.010;
RA Bouhired S., Weber M., Kempf-Sontag A., Keller N.P., Hoffmeister D.;
RT "Accurate prediction of the Aspergillus nidulans terrequinone gene cluster
RT boundaries using the transcriptional regulator LaeA.";
RL Fungal Genet. Biol. 44:1134-1145(2007).
RN [6]
RP INDUCTION.
RX PubMed=18378656; DOI=10.1128/aem.02842-07;
RA Atoui A., Bao D., Kaur N., Grayburn W.S., Calvo A.M.;
RT "Aspergillus nidulans natural product biosynthesis is regulated by mpkB, a
RT putative pheromone response mitogen-activated protein kinase.";
RL Appl. Environ. Microbiol. 74:3596-3600(2008).
RN [7]
RP FUNCTION.
RX PubMed=18029206; DOI=10.1016/j.fgb.2007.09.004;
RA Schneider P., Weber M., Hoffmeister D.;
RT "The Aspergillus nidulans enzyme TdiB catalyzes prenyltransfer to the
RT precursor of bioactive asterriquinones.";
RL Fungal Genet. Biol. 45:302-309(2008).
RN [8]
RP FUNCTION.
RX PubMed=22083274; DOI=10.1007/s00253-011-3657-9;
RA Sakai K., Kinoshita H., Nihira T.;
RT "Heterologous expression system in Aspergillus oryzae for fungal
RT biosynthetic gene clusters of secondary metabolites.";
RL Appl. Microbiol. Biotechnol. 93:2011-2022(2012).
RN [9]
RP INDUCTION.
RX PubMed=24066102; DOI=10.1371/journal.pone.0074122;
RA Ramamoorthy V., Dhingra S., Kincaid A., Shantappa S., Feng X., Calvo A.M.;
RT "The putative C2H2 transcription factor MtfA is a novel regulator of
RT secondary metabolism and morphogenesis in Aspergillus nidulans.";
RL PLoS ONE 8:E74122-E74122(2013).
RN [10]
RP INDUCTION.
RX PubMed=26773375; DOI=10.1016/j.fgb.2016.01.004;
RA Bayram O., Feussner K., Dumkow M., Herrfurth C., Feussner I., Braus G.H.;
RT "Changes of global gene expression and secondary metabolite accumulation
RT during light-dependent Aspergillus nidulans development.";
RL Fungal Genet. Biol. 87:30-53(2016).
CC -!- FUNCTION: Didemethylasterriquinone D synthetase; part of the gene
CC cluster that mediates the biosynthesis of terrequinone A, an antitumor
CC agent (PubMed:17704773, PubMed:16426969, PubMed:17291795,
CC PubMed:22083274). The first step in the biosynthetic pathway for
CC terrequinone A is formation of indole pyruvic acid (IPA) from L-
CC tryptophan by the aminotransferase tdiD (PubMed:17704773). The
CC nonribosomal peptide synthase tdiA then immediately converts unstable
CC IPA to didemethylasterriquinone D (DDAQ D), via condensation of 2 IPA
CC molecules (PubMed:17704773). The symmetric connectivity of the 2 IPA
CC molecules is thought to arise by head-to-tail dual Claisen
CC condensations facilitated by the TE domain (PubMed:17704773). TdiB then
CC catalyzes reverse prenylation by transferring dimethylallyl diphosphate
CC to carbon atom 2' of DDAQ D, to yield asterriquinone C-1
CC (PubMed:18029206). Finally, tdiC and tdiE enzymes robustly convert
CC asterriquinone C-1 to terrequinone A via a transformation involving
CC regular prenylation at carbon atom 5, which requires elimination of the
CC hydroxy group on C-5 (PubMed:17704773, PubMed:18029206).
CC {ECO:0000269|PubMed:16426969, ECO:0000269|PubMed:17291795,
CC ECO:0000269|PubMed:17704773, ECO:0000269|PubMed:18029206,
CC ECO:0000269|PubMed:22083274}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.2 uM for indole pyruvic acid (IPA)
CC {ECO:0000269|PubMed:17704773};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:17291795, ECO:0000269|PubMed:17704773}.
CC -!- INDUCTION: Specifically expressed at both asexual stages
CC (PubMed:26773375). Expression is positively regulated by the secondary
CC metabolism regulator laeA (PubMed:16426969, PubMed:17291795).
CC Expression is also positively regulated by mpkB (PubMed:18378656).
CC Expression is also positively regulated by mtfA (PubMed:24066102).
CC {ECO:0000269|PubMed:16426969, ECO:0000269|PubMed:17291795,
CC ECO:0000269|PubMed:18378656, ECO:0000269|PubMed:24066102,
CC ECO:0000269|PubMed:26773375}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CBF80711.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=EAA66857.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; EF550581; ABU51602.1; -; mRNA.
DR EMBL; BN001305; CBF80711.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AACD01000154; EAA66857.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_681782.1; XM_676690.1.
DR AlphaFoldDB; A7XRY0; -.
DR SMR; A7XRY0; -.
DR STRING; 162425.CADANIAP00003005; -.
DR ESTHER; emeni-q5at67; Thioesterase.
DR PRIDE; A7XRY0; -.
DR EnsemblFungi; EAA66857; EAA66857; AN8513.2.
DR GeneID; 2868849; -.
DR KEGG; ani:AN8513.2; -.
DR VEuPathDB; FungiDB:AN8513; -.
DR eggNOG; KOG1176; Eukaryota.
DR eggNOG; KOG1202; Eukaryota.
DR OrthoDB; 127131at2759; -.
DR BioCyc; MetaCyc:MON-18727; -.
DR SABIO-RK; A7XRY0; -.
DR Proteomes; UP000000560; Chromosome V.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0016405; F:CoA-ligase activity; IBA:GO_Central.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0019748; P:secondary metabolic process; IBA:GO_Central.
DR GO; GO:1900796; P:terrequinone A biosynthetic process; IMP:AspGD.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR001031; Thioesterase.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF00975; Thioesterase; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..970
FT /note="Didemethylasterriquinone D synthetase tdiA"
FT /id="PRO_0000436364"
FT DOMAIN 595..673
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 135..489
FT /note="Adenylation"
FT /evidence="ECO:0000255"
FT REGION 700..961
FT /note="Thioesterase"
FT /evidence="ECO:0000255"
FT ACT_SITE 774
FT /evidence="ECO:0000269|PubMed:17704773"
FT MOD_RES 631
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MUTAGEN 774
FT /note="S->A: Impairs the generation
FT didemethylasterriquinone D from indole pyruvic acid."
FT /evidence="ECO:0000269|PubMed:17704773"
SQ SEQUENCE 970 AA; 107587 MW; 7639607783AEAA89 CRC64;
MAPSKTEIAP LRAAKYPFGN IVDALRHAAA HTDEGIIVYH PNSISTSSPP QTVSYKDLLH
QAEANATRLL QQKLCSPKSI VLVHFESALD SIVWYWSVLL AGGIPALTGP GMFSQNPADR
ERHLRHLSET LNSPVCLTRP ALLAPFEEQT ADDRIKARTV DEILAAPEIA DVADAPLPAL
TPSSTDMLAL MLTSGSSGNA KAVPLTHQQL LAAFRGKSTA ASLRFPRSPF LSWVHMDHVA
NLVHCHIFAI VSGISQIQVP APDLLINPAQ LLNLISRHRV SRTFMPNFLC AKLRRQLESG
SPEYILDPGL NLETLYIDTG GEANVTEVCI ALQSLLSRYG APDNVFKPSF GMTETVAGCI
FNSHCPSYDH AQRHEFACLG KPMPGVRMRV TRLDTPSEEA APGERGSLEV TGEVVFKGYY
NNPAATAEAF TSDGWFRTGD LAFIDSNGNL HLDGRTKEMI NINGVKYLPY ELDAALEQAQ
IPGATPSYFC TFSSRDATMD TEVVVVLYLP SYVESDDEAR FSTQSSIIRV VAMHTRSRPR
VVPLRPQDMP KSTLGKLSRA KLKTALEEGQ FATQQQINDE AIRRYQQKTR ASPETPDEAV
ILDIIKEQLE IRSDDDSFGV NDSILSIGAT SMDLVAIIHR INKCLQPSQP LRLTDILKDS
TARGLAVALA TGAAPRSQDQ SSTHVYDPVV TLQPHGTKSP LWLVHPGVGE VLVFVNLAHH
ITDRPVYAFR AKGFNAAAGL PETPFTSLEE LFTTYRDAIK ERQPHGPYAI AGYSFGGMVA
FEVSKLLEQD GDEVRYCGSW NLPPHIKFRM RELVWEECVI HLFYFVGLMT ELAAYTHKPT
LQEFNRANRR LDAIRYLRQH CDAARWDELG LSEEYYLLWV GLASNMQSLA VDYEPSGSVK
CMDVFVADPL SHVAKDRIDW VEGRLSAWKE FVREDVRFHD VQGAHYTMLN REYVEAFAGT
LKNVLRERGL
