THNA_TRIHA
ID THNA_TRIHA Reviewed; 4043 AA.
AC A0A0G0AID6;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2015, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=Hybrid PKS-NRPS synthetase thnA {ECO:0000303|PubMed:33570538};
DE EC=2.3.1.- {ECO:0000269|PubMed:33570538};
DE EC=6.3.2.- {ECO:0000269|PubMed:33570538};
DE AltName: Full=Trihazone biosynthesis cluster protein A {ECO:0000303|PubMed:33570538};
GN Name=thnA {ECO:0000303|PubMed:33570538};
GN ORFNames=THAR02_03179 {ECO:0000312|EMBL:KKP04699.1};
OS Trichoderma harzianum (Hypocrea lixii).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Hypocreaceae; Trichoderma.
OX NCBI_TaxID=5544;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=T6776;
RX PubMed=26067977; DOI=10.1128/genomea.00647-15;
RA Baroncelli R., Piaggeschi G., Fiorini L., Bertolini E., Zapparata A.,
RA Pe M.E., Sarrocco S., Vannacci G.;
RT "Draft whole-genome sequence of the biocontrol agent Trichoderma harzianum
RT T6776.";
RL Genome Announc. 3:E0064715-E0064715(2015).
RN [2]
RP FUNCTION, DOMAIN, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=33570538; DOI=10.1039/d0ob02545c;
RA Zhu Y., Wang J., Mou P., Yan Y., Chen M., Tang Y.;
RT "Genome mining of cryptic tetronate natural products from a PKS-NRPS
RT encoding gene cluster in Trichoderma harzianum t-22.";
RL Org. Biomol. Chem. 19:1985-1990(2021).
CC -!- FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that
CC produces the tetronate natural products trihazones (PubMed:33570538).
CC The PKS-NRPS synthetase thnA with the help of the trans-enoyl reductase
CC thnE are responsible for the synthesis of the carboxylmethyl containing
CC trihazone A (PubMed:33570538). The PKS portion of thnA synthesizes
CC beta-keto-triene chain from one acetyl-CoA and 6 equivalents of
CC malonyl-CoA, in collaboration with thnE, which selectively reduces the
CC enoyl intermediate during the first and fourth iteration of the PKS
CC (PubMed:33570538). The NRPS domain selects and activates malate, of
CC which the alpha-hydroxyl group attacks the completed polyketide acyl-S-
CC ACP chain to form the ester product (PubMed:33570538). Intramolecular
CC Dieckmann cyclization catalyzed by the terminal reductase domain
CC releases the product as trihazone A from the PKS-NPRS
CC (PubMed:33570538). The pathway begins with the formation of trihazone A
CC by the hybrid PKS-NRPS synthetase thnA and the trans-enoyl reductase
CC thnE. Trihazone A is further decarboxylated by the 2-oxoglutarate-
CC dependent dioxygenase thnC to produce trihazone D. The function of the
CC FAD-dependent monooxygenase thnD has still to be identified
CC (PubMed:33570538). {ECO:0000269|PubMed:33570538}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:33570538}.
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. ThnA contains
CC also a polyketide synthase module (PKS) consisting of several catalytic
CC domains including a ketoacyl synthase domain (KS), an acyl transferase
CC domain (AT), a dehydratase domain (DH), a methyltransferase domain
CC (MT), and a ketoreductase domain (KR). Instead of a thioesterase domain
CC (TE), traA finishes with a reductase-like domain (R) for peptide
CC release. ThnA has the following architecture: KS-AT-DH-KR-PCP-C-A-T-R.
CC {ECO:0000305|PubMed:33570538}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; JOKZ01000069; KKP04699.1; -; Genomic_DNA.
DR EnsemblFungi; KKP04699; KKP04699; THAR02_03179.
DR OMA; HSSDQIY; -.
DR OrthoDB; 19161at2759; -.
DR Proteomes; UP000034112; 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..4043
FT /note="Hybrid PKS-NRPS synthetase thnA"
FT /id="PRO_0000455675"
FT DOMAIN 2434..2512
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:33570538"
FT DOMAIN 3614..3695
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:33570538"
FT REGION 9..443
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33570538"
FT REGION 558..894
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33570538"
FT REGION 952..1256
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33570538"
FT REGION 1417..1591
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33570538"
FT REGION 2146..2320
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33570538"
FT REGION 2521..2618
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2626..3067
FT /note="Condensation (C) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33570538"
FT REGION 3092..3496
FT /note="Adenylation (A) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33570538"
FT REGION 3736..3954
FT /note="Reductase (R) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33570538"
FT COMPBIAS 2533..2547
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2574..2605
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2472
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3655
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 4043 AA; 441739 MW; 95C213C5C8075C3F CRC64;
MGSQNLEPIA IVGSACRFPG GVNSPSALWK LLEDPKDVCT DIPSDRFDTT GFYHPDGKHH
GATNVRKSYL LQEDLRLFDT AFFNISPNEA DSMDPQQRIL LETVYEALEA GGHTMESLRG
SDTAVFTGTM GVDYNDTGIR DLNTVPTYFA TGVNRAIISN RVSYFFDWHG PSMTIDTACS
SSLIAVHQAV KALRTDESRV ALACGTQVIL NPEMYVIESK LKMLSPTGRS RMWDADADGY
ARGEGMAAIV LKRLSDAIAD GDHIECLIRH TGSNQDGYSN GITVPSTEAQ AALIRQTYAQ
AGLDPERCAE DSPQFFEAHG TGTKAGDPKE AAAIYHSFGR HKSAGDTPLY VGSIKTVIGH
LEGSAGLAGL LKASGSIQNG VIAPNLLFQR LNPDIEPFYK GLQVPTKVIP WPQLPAGVPR
RASVNSFGFG GSNAHAILEE YRGPSGQSEG TSGSQDGAIF TPFVFSAFSE SSLVAQLRAT
ADYLRTQQEK VNAKDLAWTL QSRRSQFPTK LALSALNIEE LVSKIDAKLA PLAQNPNIAI
GTKASSKAAS AGPKILGVFT GQGAQWASMG AELIRSSAFV AKRIDELEQS LAALPASDRP
QWSLKAEIMA NSDTSRIGEA ALSQPLCTAI QVVLVDLLQS AGISFSAVVG HSSGEIAAAY
AAGFFSANDA VRIAYYRGLH ARLAGNASTG QSGAMIAVGT SWEDAQDLIS LRAFKGRLAV
AAHNSAASVT LSGDADAVAH AKRVFDDEKK FARVLKVDTA YHSHHMLPCG DPYISSLQSC
VIQINKTRKD NSCAWFSSVT PSSQGMEPID ALKDTYWRDN MTNAVLFADA VKNAVASDEQ
LSLVLEVGPH PALKGPATQN IADVRPSPIP YSGVLSRGAN DVNAFSDALG FVWTHFGSQH
VDFQSYTKLV SDGERQPKLV VGLPSYQWNH ARLHWNESRR SKRLRGRKQA THEILGTILP
ESTPQDLRWS NILKVSEMPW MEGHQLQGQT VFPAAGYIAM ALEASKFLAA DKEVKVFEVN
DLAIPRAVTF EEGDTSGVET LVTLTDIRQH QNKYLAANFS CYSLPVLSSG SEQEMDLIAT
ATVKIILGTP SVESLMAPPA EDYNLFPIDA DRFYTTLEGL GYGYSGPFKA FSSMQRRLDY
ATGQVATYVY SEDDTSPYLF HPSTLDVAFH AAMLAYSSPG DERLWSLHVP TGIRSVRVNP
ALCSLLPATG TRLPVRASID GTSTSFSGYV DLLSEDGEYS AVQIEDLSIK TFAPATQADD
RVLFTHTKLD IAGPDGAAVA EGVRPTALEK ELAHACERMA YFYVRKWNSE LSDDEWANGQ
PHYKYLHDWV KRTLDLAKKG QHPTLQRKWA NDTAEEINAL MDQYPDNLDV KMIRTVGEKI
PPAVRNETTI LEHLLQDNML DDFYKLGSGF QRYNQFLASM MKQITHRYPH TKILEIGAGT
GGATKYLLKA MGDKMASYTY TDISLGFFGK AAEIFKEYSD KMTFKVLDVE KSPAAQGYEQ
HSYDIVIASN VLHATESLHT TLVNTRKLLK PGGYLLLLEI TNNNPIRTGL IWGTFAGWWL
GVEDGRRWAP TISPGQWHSA LRKAGFAGVD AVTPEIDTVA WPFSIMASQA VDDRVTFLRQ
PLSSLSPPIH IESLVILGNQ SLQTARLAEE LADNLRRFCG ELTILDSLPT DEESLDLAPQ
STFINLVDID SPIFKDITSE GMGGLQRMFE LAKHVLWITS GALIEEPYHM SSITFSRVVR
RESGHINLAH LDVSDLQQSD VPKAISKHLL QLVALDEWET PAIGADGQED QQRILWSKES
EAFLENGTLL LPRLVNNVEQ NARLNSARRT IYKEVPIRSP TVTLIPPSAT SPPSLAEPTS
LVPRRSDNLL WVDSSSLMAL NVASDSYLFL AVSKEDATGR PLLLLSTTNS VAMAPVATLE
APMDAKTYVK NPSESSSRLL VTAASEILAS SLIDRLSPGS SVLVHCSNKD RFLAAALSRR
ASPAAVMFTF TFDADDKSGT ENSAWVPLSG RASNYGIRKA MPSAKPTHFL DLTAGTGLGL
RISQLLPPTC HHIEISSLVR NESTVASSCD PDTLTNHLRE TCLGDELTSA LASEQRELKD
LIIAADHLDT SATYHATSAV FWPSTGLVKV GVSSIDSTGL FSRDKTYLLV GLTGKIGQSI
AKWLVANGAG CVCLMSRNPN IEPAWIESFQ GTGGDVKIYS MDSTDITSVE TVMNEIRTTC
PPIGGVAHGS MVLHDSLFSK MTVEDMQTVL APKIDGAIYL DQLFYDDDLD FFVLFSSAAC
VVGNLGQANY AAANGYLNSL SRQRRRRGVA GSTFDIGQVA GVGYIESAGQ IVMDQLSALG
LQRLSEADLQ QVFAETIRAG RPDPKDAETT PFAVVTSGIR NFSEDENIKG PWFTNPFFSH
CVIDAKVAEL ESDSSDKKSN IPAARQLVKA TSLEQALDIL KECFATKLRV ILQLGSQDID
YDAPLVELGI DSLVAVEVRS WFLKEVRVDI PVLKVVGGAS LAELCDRVVD KLPEELLVSV
GKQGESQPPA STAQPQPVAP KPKPLPVPSF VVDSNGPPSE VSVSPAGTPL LSAGPASYSA
TEASTRSGSP SEATRLSQKV SSKLQSYFPP PPEPAVERKR PAKRFIKSVP ISLGQSRFWF
LQQLLDDQRT HNVAYYYHIK GNLDVGDMER AVRLVASRHE ALRTCFVQDE TDASQAYQKV
LPSSPVRLIC KKIDSEDDVA SEYQRLRAHD LDMASGELLK LVLLTLSPSS HFLLMYHHHI
IMDGISLQVF LSDLEKAYKG ESLGPAPKQY PDFSKAQRQA FENGEMKKEL AFWRRIFPDG
EQPPVLPLLP MARTNARVPM AKFDTHQVQA RVDAALAAKV RTVAKQQRST PFHLYLAAFK
ALLFCFTDVD ELTIGVADGA RHDSSLMGSI GFFLNLLTLR FRRQPNQPFT EAIAEARKIS
HAALENSRVP FDVLLSELNV ARSSTYSPFF QAFIDYRQGH QEEQTWGNCQ MRMSEEVHTG
KTAYDITVDV TETDAAAFIF FRGQKSIYDQ EATQLLCDTY VHFLEVLTKE PSLAMSAIPR
FSEKQLAEAI QVGRGPKLVS DWPETLPLRI DQVARENPDK VALMDGTGKA LTYASMINRI
HSIAEALQEA GVGPGLRVLV FQQATSDWPC SMLAIMRLGA IYVPLDLRNP LPRLAAVAQD
CEPTAILADA STLDEASQLG VPSARLIDVS LVKTNPSKEV SNDSRAHSTA AILYTSGSTG
TPKGIMVTHE GLRNEIEGYT KTWKLGPERV LQQSAFTFNH SSDQIYTGLV NGGMVYVVPW
DKRGNALEIT KIIQEQGITY TKATPSEYSL WMLYGRESLR LATSWRCAFG GGESLTTTVT
QQFADLDLPQ LHFFNSYGPT EISISSTKME IPYRDREALE RVGRIPCGYS LPGYYMYAVD
EELRPLPAGM PGQLCIGGTG VSLGYLKNQE LTDKHFLPNP FATEEDIANG WTRMYLTGDI
GHMNQDGTMV FHSRMAGDTQ VKIRGLRIEL SDIESNIVAA SQGALREAVV TLREGDPEFL
VAHVVFVPEC TIADKETFLQ QLLHNLPVPQ YMIPVVAIPI DELPLTNHSK VDRKAVKSLP
LPHRVDRPDT SDDTELTETM IQLKGLWRGV LGKAIDQLGF DITPFTSFFL VGGNSLLIIR
LQSEIRKRFR AAVPLVELLG ANTLGEMAQK VEETISVKTI DWEYDTRPPT ISASAIASAI
ASVPIDRARK GSTIVITGAT GFLSKHLLPM LDARTDVDVI HCLAVRDIER AYSSPKVIHH
SGDLSSPLLG LSNDEFNELS GTADAILHMG AARSFWDSYH VLRPINVAPT SDLVKLAAPR
RVPIHYISTA SLFGGTTATL DGSAVSAAAY PPPTDGSSGY AATRWASERI LERSAADLGV
PSSIYRLCPA TTRQDAPQAL LDEFTHYGSI IRATPDLSGW SGRLDMLPAV LTAQWLCEAL
LNYEERSGIV QFRNYESLLT VTGAELTASF DQEQSGSGNL EKISLLKWIG KIKKAGFPYF
LASHEIAIEK EGSVNDTKLE MRR
