ILIA_HYPJQ
ID ILIA_HYPJQ Reviewed; 3812 AA.
AC G0REX6;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 1.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=Hybrid PKS-NRPS synthetase iliA {ECO:0000303|PubMed:34947016};
DE Short=PKS-NRPS iliA {ECO:0000303|PubMed:34947016};
DE EC=2.3.1.- {ECO:0000269|PubMed:34947016};
DE EC=6.3.2.- {ECO:0000269|PubMed:34947016};
DE AltName: Full=Ilicicolin H biosynthesis cluster protein A {ECO:0000303|PubMed:34947016};
GN Name=iliA {ECO:0000303|PubMed:34947016}; ORFNames=TRIREDRAFT_58285;
OS Hypocrea jecorina (strain QM6a) (Trichoderma reesei).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Hypocreaceae; Trichoderma.
OX NCBI_TaxID=431241;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=QM6a;
RX PubMed=18454138; DOI=10.1038/nbt1403;
RA Martinez D., Berka R.M., Henrissat B., Saloheimo M., Arvas M., Baker S.E.,
RA Chapman J., Chertkov O., Coutinho P.M., Cullen D., Danchin E.G.,
RA Grigoriev I.V., Harris P., Jackson M., Kubicek C.P., Han C.S., Ho I.,
RA Larrondo L.F., de Leon A.L., Magnuson J.K., Merino S., Misra M., Nelson B.,
RA Putnam N., Robbertse B., Salamov A.A., Schmoll M., Terry A., Thayer N.,
RA Westerholm-Parvinen A., Schoch C.L., Yao J., Barabote R., Nelson M.A.,
RA Detter C., Bruce D., Kuske C.R., Xie G., Richardson P., Rokhsar D.S.,
RA Lucas S.M., Rubin E.M., Dunn-Coleman N., Ward M., Brettin T.S.;
RT "Genome sequencing and analysis of the biomass-degrading fungus Trichoderma
RT reesei (syn. Hypocrea jecorina).";
RL Nat. Biotechnol. 26:553-560(2008).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, DOMAIN, AND PATHWAY.
RX PubMed=34947016; DOI=10.3390/jof7121034;
RA Shenouda M.L., Ambilika M., Cox R.J.;
RT "Trichoderma reesei Contains a Biosynthetic Gene Cluster That Encodes the
RT Antifungal Agent Ilicicolin H.";
RL J. Fungi 7:0-0(2021).
CC -!- FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that
CC mediates the biosynthesis of ilicicolin H, a 4-hydroxy-2-
CC pyridonealkaloid that has potent and broad antifungal activities by
CC inhibiting the mitochondrial respiration chain (PubMed:34947016). IliA
CC assembles the backbone of ilicicolin H (PubMed:34947016). The PKS
CC portion and trans-acting enoyl reductase iliB work together to
CC construct an octaketide, and two methyl groups are introduced by the MT
CC domain during the chain assembly (PubMed:34947016). The nascent chain
CC is then condensed with tyrosine, catalyzed by the C domain, and the
CC resulting PKS-NRPS hybrid is offloaded by the RED domain to form an
CC advanced tetramic acid intermediate (PubMed:34947016). The biosynthesis
CC of ilicicolin H starts with formation of the tetramic acid by the
CC hybrid PKS-NRPS synthetase iliA with the partnering trans-enoyl
CC reductase iliB since iliA lacks a designated enoylreductase (ER)
CC domain. The cytochrome P450 monooxygenase iliC then catalyzes the ring
CC expansion of the tetramate to the acyclic 2-pyridone. The pericyclase
CC iliD further converts the acyclic 2-pyridone into 8-epi-ilicicolin H.
CC 8-epi-ilicicolin H might then spontaneously convert to ilicicolin H to
CC ilicicolin H since ilicicolin H is produced in the absence of the
CC epimerase iliE, in contrast to what was observed for the Talaromyces
CC variabilis ilicolin H biosynthetic pathway (PubMed:34947016)
CC (Probable). {ECO:0000269|PubMed:34947016, ECO:0000305|PubMed:34947016}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + 8 AH2 + ATP + 4 H(+) + holo-[ACP] + L-tyrosine +
CC 7 malonyl-CoA + 2 S-adenosyl-L-methionine = 8 A + AMP + 7 CO2 + 8 CoA
CC + diphosphate + 6 H2O + N-[(4E,6E,10S,12Z,14E)-6,10-dimethyl-3-
CC oxohexadeca-4,6,12,14-tetraenoyl]-L-tyrosyl-[ACP] + 2 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:64544, Rhea:RHEA-COMP:9685, Rhea:RHEA-
CC COMP:16623, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:17499, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:57856, ChEBI:CHEBI:58315,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:64479, ChEBI:CHEBI:155893,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:34947016};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64545;
CC Evidence={ECO:0000269|PubMed:34947016};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:34947016}.
CC -!- DOMAIN: IliA has the following domain architecture: KS-MAT-DH-MT-KR-
CC ACP-C-A-T-R. The PKS module (domains KS to ACP) is responsible for the
CC biosynthesis of the polyketide chain and catalyzes three Claisen
CC condensations, as well as beta-keto processing and methylation. The
CC downstream NRPS module contains the condensation (C), adenylation (A),
CC and thiolation (T) domains and catalyzes the formation of the L-
CC tyrosinyl-thioester and the amide linkage between L-tyrosinyl-thioester
CC and the tetraketide. The bimodular assembly line is terminated with a
CC putative reductase (R) domain that facilitates formation and release of
CC the tetramic acid product. {ECO:0000305|PubMed:34947016}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; GL985060; EGR50286.1; -; Genomic_DNA.
DR RefSeq; XP_006963788.1; XM_006963726.1.
DR STRING; 51453.EGR50286; -.
DR EnsemblFungi; EGR50286; EGR50286; TRIREDRAFT_58285.
DR GeneID; 18486265; -.
DR KEGG; tre:TRIREDRAFT_58285; -.
DR VEuPathDB; FungiDB:TRIREDRAFT_58285; -.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_37_4_1; -.
DR Proteomes; UP000008984; Unassembled WGS sequence.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase 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; -; 2.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.12780; -; 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; 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; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
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; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR013968; PKS_KR.
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; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 2.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Ligase; Methyltransferase; Multifunctional enzyme; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat;
KW Transferase.
FT CHAIN 1..3812
FT /note="Hybrid PKS-NRPS synthetase iliA"
FT /id="PRO_0000455711"
FT DOMAIN 2229..2306
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3361..3440
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 15..448
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:34947016"
FT REGION 559..883
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:34947016"
FT REGION 952..1258
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:34947016"
FT REGION 1398..1597
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:34947016"
FT REGION 1941..2082
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:34947016"
FT REGION 2383..2813
FT /note="Condensation (C) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:34947016"
FT REGION 2847..3243
FT /note="Adenylation (A) (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:34947016"
FT REGION 2847..3243
FT /note="Reductase (RED) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:34947016"
FT ACT_SITE 186
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2266
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3400
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3812 AA; 417686 MW; DE7716C383776851 CRC64;
MDQQRQQDGR FREPIAVIGS ACRFPGACSS PSKLWDLLQQ PRDVLKEFHP ERLNLSRFHH
KSGDTHGATD VGNKSYLLEE DTRLFDAAFF GISPIEAAGM DPQQRILLEA VYETFESAGV
TLDELRGSFT SVHVGCMTSD WANIQARDTE TVPKYNATGS ANSILSNRIS YIFDLKGPSE
TIDTACSSSL VALHNAARGL LNGDCNAAVV AGVNLILDPA PFINESKLHM LSPDARSRMW
DKDANGYARG EGAGALLLKT LSQALKDGDH IEGLVRATGV NSDGQSPGIT MPYSPTQTAL
IQQTYARAGL DPIKDRPQYI ECHGTGTPAG DPVEARALSN AFIGHVDKST ENPILVGSIK
TVIGHLEGGA GIAGVIKVLL SIKYRVIPPN LLFKDLNPDI APYYGPLQIP TTAVPWPELP
PGTPARASVN SFGFGGTNAH AVIESFDESF GPRASSADEG VVGPLLFSAK SGASLLRSVR
DNLEYLQKDA SLDLRDLSAF LQSRRTTHRV RAHFTGSSRD AVLENMTNFI TTHAQSASDQ
IGHQPQLINP KEVPGVLGVF TGQGAQWPAM GRELYCKSAL FRKTIEECEA VLDALPQQDR
PDWSLTEELM KDAISSRISE AALSQPLCSA VQLALVKLLQ AAGIAFDAVV GHSSGEIAAT
FAAGIITLQG AMQIAYYRGL HAKSAGGANH AKGAMMAVGL SFAEAKQFCS RPEFDGKIKV
AASNAPKSVT ISGDVDAIVQ AHEILQADNI FARRLQVDTA YHSHHMLPCC QPYLNSLLAC
NIKVMQPTGK CTWISSVRGD TQLLRGDLSS LKGQYWVDNM VRTVLFTQAI ESSIWHGGPF
DLAIEVGPHP ALKGPTEQTL KASYGILPVY TGVLKRGENN VEAFSAAVGT TWAQLGPAFV
DFAGYRNLFY EAETPVFKIP KGLPLYSWDH DKVFWREGRL SRRFRLGNDQ GHELLGRRTL
DDNDTELRWR NVLKLGEMPW LRGHEVLGEV LLPGASYVSV AVQAGHNIAM TMGKNVRLIE
ISNVDILRPV VVPEGTDGVE TLFTTRIVET TRDHIKAEFM YYVCPDESLG TMLRTCNGEV
MVYLETQTDI ASPDTLPAKD AMPLNLTKID TERVYSLFKD IGLNYSGLFR GISTIERKLD
YASTRSTWVD GLDSAYVVHP AMLDVAFQTM FIAKAHPASR QINSALLPSH IDRVRINPSV
QFTQPNEVAE TAAEFETWAV KQTANSLVGD LNIYDAATGK TFLQVEGLAV NSVGEQDASS
DNSMFSRTLW GQDVTLGLPD PVRDPVKDAE GLQMAHAVER VAVFYVKNIL KEVKKEERAD
FQWYHQRMFE AFENHISIVK NGEHPIILPE WLDDEESILD ELDSKHGDTI DFKLLHAVGK
DLAHVVRGNK QMLEVMTKND MLNRFYMEGY ASVPTNKAVG DVMRQLSFKF PRAKILEIGA
GTGGTSWSVL KSINDAYESY TYTDVSSGFF HLAEEKFSDF AHKIIFKVLD IEQEPKEQGF
KEQSYDIIIA ALVLHATHDL ERTMRHARSL LKPGGFLVMV ELTGTMSVRA TLVMGGLPGW
WLGENDGRRL SPLVTAIEWD RLLQNTGFSG ADAVIHDLAD EEKHCTALIM GQAVDDDFQR
LRSPLSTVAE LPPPDDPILV IGGKRLSTSK VIREIQKLFP RKWARHVRVY KSIDEVNVSG
ITPGLDVLSL QDLDESPFSH TITAHELFIM AGRSGSSWVA AVTNANTSIA RVHGTHVIPI
DEQDCSPERL SAIANYILSW SISTVAGPHA SVLLFEAHDS LAASVKAQLA AAGGKAFFAS
TRTHGTPANG IKIHALASKR SIQRVVPHDV QLFIDCSLDS SPAAATLTQS MPSNCISRQL
DVQLVQEALR SAHRESVELL KEAFAFPGVE SPAVPVVPAQ TLAGRSFMSL KAQAYVTDWT
TQVISTTVPP LSLEGLFRPD KTYFMAGMAG GLGLSICQWM IRNGAKHMVI TSRNPQVNTA
TLEEAERVGA TVKVLAMDLT NRESVEKVVQ QIRETMPPIA GVCNAAMVLK DGFFVDMDVD
QFNNTLAAKV IGSENLDSVF SSTPLDFFIL LGSVASVIGN VGQSNYHAAN LFMDSLVHQR
RARGLAASIV HIAYVTDVGY VTREERDRQL DSHFRKVRLM PTSETDVHHA FAEAVKGGKP
GSTSGYHDII MGIEPLREQI PLDQQPLWMK NPRFAHFDQH AIHAQHERGS TGSIDNVRAL
VEKAEKEEEA IDAVMAAFCA KLESILQLTA GCINVQRPIT DLGIDSLVAV EIRTWFLKEL
GADVPVVKIL GGDTVQQLST IATKKLLAKN MEAGAEKKST IEKPAEATAP VPTSKQEESI
SSNSSYTKDD TPELEDEYES SVGVAAEEAD EMRVRPGIIR EERMSPAQAR LWFMSQHLEN
SAAYNMAFRY KVKGPIGTAR LKHALSFTTH KHECLRMCFY SHLEDGHPMQ GLMASSLCNF
KHTVHASEDD VAREMSRLST CQWNLQYGHT MEVSLLSRDS EDHDLIIAYH HIVMDVIGLG
VVLDDLNNAY NMKPVNKSAG SYIEFSVKQL EQQARGDFDK QLSFWEAEFR TIPQRLPRLP
FARIGSPSGV AESVPDTYHQ YRELNDTQFA SLKATCQKLR ISPFHFHLSL LQVLLSRYTN
TDDLCIGIVD ANRNDHRYAG TVGCFVNMVP VRLHVPPGKA SFADVAQQTR RSALQALEHS
AVPFDMILDK IKAPRSSRST PLFQAALNYR TGSIWELPLG RAKMTMADVK DANNPYDLSL
GIAETRTGCM VEVYVSSSAY GAEACATIMD AYMRLLDDFS NTPDLQINDC NIYGKPEIDS
SLSIGQGPVI HFEWPATLSQ RFLDMVRLHH GDPAVTDKTG TLTYSELLER VNGVSDTLIR
HGCKSGTRIA VLCEPSIDTI VAMLAILHIG AVYVPLDVSL PTARHVAMIQ SSKPSFVVNH
ASTDGQAREC IGKIEFPIRR VVLDDVIEEE IRVTVPCLAS PDACSIVLFT SGSTGTPKGI
MLSQANFANH LALKTHLLGL GKETVLQQSS TGFDMSIVQM FCALANGGRL VIAPFDIRRD
PIEMVSLVCS EHISLSIATP SEYLAWTRYG ISSLKENTAW RHICMGGESV TRQLVLELRR
LGLPNLRVTN CYGPTEITAA ASFQPIDLGG QEDAHPDMVK YKVGKVLPNY TVSILDARGS
PQPVNHTGEV CIGGAGVALG YISASDDAAS KFIVTAQGQR MYRTGDRGRL LSDGTLLLFG
RIEGDSQIKL RGIRVDLQEV ELAVLEAADG LLSNVVVSQR GDVLIAHATV PPGEPEATLI
TEDDLNRVLR RLDLPQYFIP ARIVILSSLP TNANGKLDRK AIAALPLPSC QSRADSGSEE
EKMTIEEGEL RLLWERVLPQ VAPLTRIAPS SDFFLLGGNS LLLMKLQAAM KDSMNVMMST
RKLYQASTLR EMARAVDKQR RSQAEHDDQR EIDWAAETAI PKWLLNQIHE QSQSKQVVGA
KSPVEKISVL MTGATTFLGG HLLKSLLESD KVSKIYCIAV LADDQHLLPE NEKIESFNGS
LLSPTLGLDA TERVRLESTA DIIVHAGGSG HCLNTYATLR IPNVISTHFL ASMALPRSIP
LLFLSSSRVV LLTGNTSPPA ASVSGFPPAT DGREGHMMSK WTSEVFLENL VGHLLASSPR
HQQNPWTVSV HRPSVIVSEH APNSDALNAI LRYSILMQSS PRMDNVVGYL DLAQLDTVIA
ELRQSVIQLG SGQGKQESTN ILFKHHSGGI KVPASELWSH LGKVYGITFD EVELDEWLRR
AARAGIDPLI TAYLEAIQAN GAKMIFPYMG SD
