TASS_HAPIR
ID TASS_HAPIR Reviewed; 4061 AA.
AC A0A0F7GFS4;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2015, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=Hybrid PKS-NRPS synthetase tasS {ECO:0000303|PubMed:25885659};
DE Short=PKS-NRPS tasS {ECO:0000303|PubMed:25885659};
DE EC=2.3.1.- {ECO:0000269|PubMed:25885659};
DE EC=6.3.2.- {ECO:0000269|PubMed:25885659};
DE AltName: Full=Tetramic acid Sch210971/2 biosynthesis cluster protein S {ECO:0000303|PubMed:25885659};
GN Name=tasS {ECO:0000303|PubMed:25885659};
OS Hapsidospora irregularis.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Hypocreales incertae sedis; Hapsidospora.
OX NCBI_TaxID=95324;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, DOMAIN,
RP AND PATHWAY.
RX PubMed=25885659; DOI=10.1021/acs.orglett.5b00715;
RA Kakule T.B., Zhang S., Zhan J., Schmidt E.W.;
RT "Biosynthesis of the tetramic acids Sch210971 and Sch210972.";
RL Org. Lett. 17:2295-2297(2015).
CC -!- FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that
CC mediates the biosynthesis of the tetramic acids Sch210971 and
CC Sch210972, potential anti-HIV fungal natural product that contain a
CC decalin core (PubMed:25885659). The PKS module of tasS together with
CC the enoylreductase tasC catalyze the formation of the polyketide unit
CC which is then conjugated to 4-hydroxyl-4-methyl glutamate (HMG) by the
CC condensation domain of the tasS NRPS module (PubMed:25885659). One
CC unique structural feature of Sch210971 and Sch210972 is the tetramic
CC acid motif proposed to be derived from the non-proteinogenic amino acid
CC HMG, by a Dieckmann-type condensation catalyzed by the reductase domain
CC of tasS (PubMed:25885659). The aldolase tasA catalyzes the aldol
CC condensation of 2 molecules of pyruvic acid to yield the intermediate
CC 4-hydroxyl-4-methyl-2-oxoglutarate (HMOG), which can then be
CC stereoselectively transaminated, may be by tasG, to form HMG
CC (PubMed:25885659). The Diels-Alderase tas3 then uses the Dieckmann
CC product of tasS as substrate and catalyzes the Diels-Alder
CC cycloaddition to form the decalin ring of Sch210971 and Sch210972
CC (PubMed:25885659). {ECO:0000269|PubMed:25885659}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S,4S)-4-hydroxy-4-methylglutamate + ATP + 11 H(+) + 8
CC malonyl-CoA + 8 NADPH + 3 S-adenosyl-L-methionine = (2S)-3-[(2S)-3,5-
CC dioxo-4-[(2E,4R,6R,8E,10E,12E)-4,6,12-trimethyltetradeca-2,8,10,12-
CC tetraenoyl]pyrrolidin-2-yl]-2-hydroxy-2-methylpropanoate + AMP + 8
CC CO2 + 8 CoA + diphosphate + 6 H2O + 8 NADP(+) + 3 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:67264, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:57856, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:167901, ChEBI:CHEBI:167907,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:25885659};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67265;
CC Evidence={ECO:0000269|PubMed:25885659};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:25885659}.
CC -!- DOMAIN: NRP synthetases are composed of discrete domains (adenylation
CC (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation
CC (C) domains) which when grouped together are referred to as a single
CC module. Each module is responsible for the recognition (via the A
CC domain) and incorporation of a single amino acid into the growing
CC peptide product. Thus, an NRP synthetase is generally composed of one
CC or more modules and can terminate in a thioesterase domain (TE) that
CC releases the newly synthesized peptide from the enzyme. Occasionally,
CC epimerase (E) domains (responsible for L- to D- amino acid conversion)
CC are present within the NRP synthetase. CcsA contains also a polyketide
CC synthase module (PKS) consisting of several catalytic domains including
CC a ketoacyl synthase domain (KS), an acyl transferase domain (AT), a
CC dehydratase domain (DH), a methyltransferase domain (MT), and a
CC ketoreductase domain (KR). Instead of a thioesterase domain (TE), tasS
CC finishes with a reductase-like domain (R) for peptide release. TasS has
CC the following architecture: KS-MAT-DH-MT-KR-PCP-C-A-T-R.
CC {ECO:0000305|PubMed:25885659}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; KP835202; AKG54858.1; -; Genomic_DNA.
DR SMR; A0A0F7GFS4; -.
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; 3.
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; Repeat; Transferase.
FT CHAIN 1..4061
FT /note="Hybrid PKS-NRPS synthetase tasS"
FT /id="PRO_0000453332"
FT DOMAIN 2437..2516
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3633..3712
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 10..475
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 586..911
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 977..1280
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1425..1619
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000255"
FT REGION 2153..2325
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255"
FT REGION 2527..2617
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2632..3077
FT /note="Condensation (C) domain"
FT /evidence="ECO:0000255"
FT REGION 3103..3510
FT /note="Adenylation (A) (KR) domain"
FT /evidence="ECO:0000255"
FT REGION 3813..3969
FT /note="Reductase (RED) domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 2538..2552
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2553..2617
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 180
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2475
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3672
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 4061 AA; 443958 MW; AC30A0B1193CE6B8 CRC64;
MTKIQEQEPI AVIGMACRFP GGSDTPSKLW ELLQKPRDLS KRVPEDRFDS TGFFHENGTH
HGATDCRDAY FLEEDVTRFD NAFFNIQPGE AEALDPQQRL LMETVYESLC TAGQTVEGLR
GSRTAMYVGL MCDDWSQMTS RDWDLVPTYT ATGTSRAVMS NRISYFFDWH GPSMTVDTAC
SSSLVAVHQG VTSLRNGEAP IAVAAGANLI LAPGMWIAES NLHMLSPTGT SKMWDAAADG
YARGEGIAAV VLKPLSAALR DGDNIDCIIR ETGVNQDGRT AGLTMPSNTA QSQLIRDTYR
RAGLDINDPK DRPQFFHAHG TGTPAGDPQE AEAISRAFFD KSDVKDPLYV GSIKTVIGQA
DIVGWWDSPP PPNRHTEGTA GLASLIGTTL AMKHGTIPQN LHFNTLSDRV APFCAHLRVP
AKSLPWPSPV TGQPRRASIN SFDQWKKERT ADSDFLPQIG FGGTNAHAII EGYEPEQPPH
LVTGPTTTKT SLFTPLTISA TSSSSLRSML SDLQKYLVNH PDTNLRDVAY TLQSRRSTFS
YRRSVVCRSA DDAVNRIEGL LVDTSAENGL NSRYADVSNP SSILGVFTGQ GAQWPRMGAW
LIEESPFVAQ RLDELDEALA TLPEGDRPDW KLSEQLLADA SASRLSEAAI AQPLCTAVQV
VLVDLTRAAG IHLRAVVGHS SGEIGAAYAA GFLSATDAIR VAYYRGVYAK LSRSPKDESI
KGAMMAAGTS YEDALELCAL EEFEGRLQVA ARNSSSSVTL SGDEDAIDEV VEILKDEGRF
ARKLKVDTAY HSHHMQACAA PYLAALERAN ITAKDGNGTT WYSSVVDGQV MTKNIIQQSQ
YWVDNMTNAV LFAPAVTAAV AQAGPFDIAI EFGPHPALKG PCLDTVEEAA GSKIPYTGLL
ARQKNDVEEL LAALGFLWTH LGAGSVNFDG FENAISGASS PRRLVSTLPA YPFDHSRSFY
TLTRFSGGHQ NMHSPLHPLL GRRCVETEAD DEVSWRNILR SSENIWLQGH ALQGQAVFPA
MGYIAMAVEA AASLAGPDRR LGLISLEDVV IGRAMAFGDE SVGMEAKVAL KVSHFADDEL
RGKITCHSGL PHDSATPLAL NFSATVNVTF HEPEAESLPA VRTDEINLAN AEPQRLYSQF
NKLGYNYSPP FTGVTSVHRK KGFATGTIED ISGDNWEDQL IVHPGLLDSA LQTAFAAYCH
PHDNRFWTLH VPTAIRSIVI NPYFTDRGAG RHRQFEYQSS CRDGLESPVE ADINVFAGQG
QPHAFVQFES VRVQPFSVAG PQDDALIFSR FDYKLAEPDA TVVVEGEGLP PPDADVIFQT
IERVGFFYLR RIHETITPAE AAATLPHYKL LIEFTGRVVP RVAAGEHPTV PKEAMGDTTA
YINSLLAKYR HRSDMQLIGI VGENIIPEIR RSGSMIEHML QDGVLDRFYE EGFEYANIWI
ARVIAQIAHR HPRMDIFEVG AGTGGSTRAI LPKLGDAFAS YTFTDLSAGF FERANDRFIN
YADRMIYSTY NMENSPAEQG FEEGSYDVVL ASNALHATGK LDETISNARR LLRPGGYLVL
VEIMGNDFLG IGCSMGGLPG WWAGAAVDPT RSDGPCLNVN QWDALVRRHG FNGVETHTPL
DRKLQWYAVL VCRAVDDRVV SLREPLSTTS PVPVSAADEL VVVGGRTPAV ASLVKESTEL
LKTRYTTITH IETLEEFNTT PLSQGSSVLS LTELDEQFLE VRTEAKLEAL KTLWRNGRTI
SWVTRGARKE NPHTSSMVGL ARVMRYEYPH LNLQIVDYDR LPESKAIAES LLRLELGKTW
ESENLLWTVE PELHYVDGQL FIPRLYPYDE ANKRWNTSRR TVTTEVDPHE TTVVLEPSTD
GNTVKPCAIS PLRVRSDPPR RSSGKQITIR LQQSLLQSIK VGEAGFFTLC AGTDEESGES
LVAFVDTPAE SSVQVPVEWT VKTTEAADGS TALGYAATHL LAQSIIAAAV PRFGTLVVHE
ASSLLKDALD KEAAAEGIQV VFTTAEKTGK VDDGTVHIHQ RLPARLVRKL LPRDVSVFVN
LSPAPGASEL LRSCLARHTA TATVEDFVRI QPHISPNADI WEAGQALKTT WNAVTRHRRR
TSNLEISKVI SLNEANSVNP VEGPLTVVDW NTKSVEVALR PIDHGTIFRA DGTYFLLGLS
GELGQSLCSW MVSHGARNVV LSSRSPKVDP RYIEELAAQG ANVRALACDI TRRESLRACY
DTIRAEMPPI IGVANGAMIL EDVMFDDLEF ESQERAMPPK VEGSLYLDEL FYDTPLDFFV
LLTSLAHIGG NTGQSTYVMA NLFMVALAAQ RRDIRGVVGS DMAIGSVTGM GFFERSALDK
DHFSRMGYRN MSEQDLHTQF AEAILAGKPG AKGIPEVAIG LQPYRDTPNI QAQLRMDPRF
KHYLLQDRGA NTQGQAGGSQ GNAKPRVRLA SVTTRAEAIK VVFDTFVDRL KRILLMSATE
VIDPMVSLVE LGADSIMAVD VRGWFLKELD VDVPVLKILG PGETIALLVE EAVDKLPVDI
VDISKLEHGG EPDLTQTAPA PKPEPVRQPE LPPQPTSAAS SSDTGSDSSP TSNSVSETQT
GTPLETPMST TEAGYFKQES QQLQQKLQKH QEQTSQSWRQ KVVESSTEHT EQMTFGQNRF
WFLTHYVDDP TTFNIAYVGK LTGRIRVDDL SKAVQAAAQR HESLRTRFFW SDDDTKTPMQ
GILSNTLVRL ETATIKSAAE AAQELDEMRA YVWDLGDWVP LRMRLLSLSD TEHFLLIGTH
HISMDGHSFS VLMLDIQQAY NSPGQRLAPL PVASQARAFG AHQRLSYETG KFKTAIEHHR
SQLPAADLVR PIELFSFART QVRPALDHYG THVAKTHLPL ATAAKLKQLA RGHRATAFHA
YLAGLQALLF RLLPAATTDK VFVGLADANR LDSKFMGSIG NFLNVLPVRF DRADRQTFGQ
AMEVARDRAY GGLKHSALPF DLLLDELEVP RSNAWAPVFQ IFMDYRLVVK EHANKDWIGC
KISEENWHTS RSGYDVALEI MEGHDGAMVA MHVQKALYDA SAADLLLKTY VNVLNQVAAK
GDKFVVKELA TWDTESEQKG LATGHGPNLT LEWPATVAHR IDQVIADHPD AVALKDGHGR
SLTYKEMDER VESIAHTLRE HVPRTDKQPI VGVLQTPSAD WMCSLLAILR FGGIYLPLDL
RNGAPRLKSN VDAARPVAVL TDASSAGQVT DVCHHSDVVV INVSHLPAST GLPRMETTAA
TADGSAYIIF TSGSTGEPKG IVVKHSGLRA NLEGYHREWA IDTMSDVVLQ QTALSFDASL
VQIFAALTTG GSLFVVPADA RGDPSEVTKL MVENGVTMTQ ATPSEYDMWF RFAPETLHRC
STWKAAWFGG ERAGPSVLDG FRKACRAIPS LRVFTSYGPT ESTISAMKGE ADVRNPDLRV
PVPGRLLPNY AAYIVDDTLQ PVPTGVPGEI VLGGAGVGAN EYLNQKDMTD KQFPRDKFTS
RGDSGWGRMY RTGDYGRLDA RGYLTVEGRI AGDTQVKLRG FRIELAEIER VMVKEADGTI
SDAVVTLRGE GEQEGFLAAH VVFNGKIQGD KETGEAVDKL RARLPLCLPQ YMCPAVIVPL
DSLPLTSHHK VDRKALQTLE LPKVEASVAE QLQNLTATER TLADLWDSLL PPRAAADALG
PRSHFFSSGG NSLLLVKLQA AIKRDFGDAP RLSKLMSAPE LGSMAALLDD GVGRVNWDKE
IALDDELHGA SWRARVTPAG ADGISVLITG ATGSLGRRIT QRLANDNRVS RVVCLVRPVD
GRDMANVFPG IGDKVQIMPA DLPTLPADSD IPDIDVVLHC AADRNFWDGY HAVKPVNVDT
AKALARLCLR RGATLHVLSS GAMAAYEGDD KTPGGSLPRP TPDDGYLSSK WVAERYLAGV
ARETGLPLTA HRPTRVSDAE ALRVEQMGKT EMGMAKIMLS LSEKLNVRPD FTNLGGIIDL
SPLEDAVEAV TQAVTTNIRE EASGIRIINH AGTARMRTNA LAAHAEELFG RAENSAVMGL
PSVSALHWVG LAKRAGLFEW FFTAQDLVVE DGEGNTIASR R
