PVHA_TALVA
ID PVHA_TALVA Reviewed; 4023 AA.
AC A0A3T0QHT6;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 1.
DT 03-AUG-2022, entry version 19.
DE RecName: Full=Hybrid PKS-NRPS synthetase pvhA {ECO:0000303|PubMed:30609896};
DE Short=PKS-NRPS pvhA {ECO:0000303|PubMed:30609896};
DE EC=2.3.1.- {ECO:0000269|PubMed:30609896};
DE EC=6.3.2.- {ECO:0000269|PubMed:30609896};
DE AltName: Full=Varicidin biosynthesis cluster protein A {ECO:0000303|PubMed:30609896};
GN Name=pvhA {ECO:0000303|PubMed:30609896};
OS Talaromyces variabilis (Penicillium variabile).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Trichocomaceae; Talaromyces.
OX NCBI_TaxID=28576;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, DOMAIN,
RP AND PATHWAY.
RC STRAIN=HXQ-H-1;
RX PubMed=30609896; DOI=10.1021/jacs.8b12010;
RA Tan D., Jamieson C.S., Ohashi M., Tang M.C., Houk K.N., Tang Y.;
RT "Genome-mined Diels-Alderase catalyzes formation of the cis-
RT octahydrodecalins of varicidin A and B.";
RL J. Am. Chem. Soc. 141:769-773(2019).
CC -!- FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that
CC mediates the biosynthesis of varicidin A, an antifungal natural product
CC containing a cis-octahydrodecalin core (PubMed:30609896). The PKS
CC module of pvhA together with the enoylreductase pvhC catalyze the
CC formation of the polyketide unit which is then conjugated to L-
CC isoleucine by the condensation domain of the NRPS module
CC (PubMed:30609896). Activity of the Dieckmann cyclase domain (RED) of
CC pvhA results in release of an acyclic tetramate (PubMed:30609896). The
CC cytochrome P450 monooxygenase pvhE then catalyzes the oxidation of the
CC C21 methyl group to a to carboxylate group (PubMed:30609896). The
CC methyltransferase pvhD then further methylates the pvhE product
CC (PubMed:30609896). The Diels-Alderase pvhB is able to catalyzes Diels-
CC Alder cycloaddition using both pvhE and pvhD products as substrates to
CC form the decalin ring, yielding varicidin B and A, respectively
CC (PubMed:30609896). {ECO:0000269|PubMed:30609896}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:30609896}.
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), pvhA
CC finishes with a reductase-like domain (R) for peptide release. PvhA has
CC the following architecture: KS-MAT-DH-MT-KR-PCP-C-A-T-R.
CC {ECO:0000305|PubMed:30609896}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; MK376933; AZZ09613.1; -; Genomic_DNA.
DR SMR; A0A3T0QHT6; -.
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; 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.
PE 1: Evidence at protein level;
KW Ligase; Methyltransferase; Multifunctional enzyme; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Repeat; Transferase.
FT CHAIN 1..4023
FT /note="Hybrid PKS-NRPS synthetase pvhA"
FT /id="PRO_0000453333"
FT DOMAIN 2404..2479
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3593..3670
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 10..443
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 550..871
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 945..1249
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1402..1585
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000255"
FT REGION 2120..2291
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255"
FT REGION 2490..2580
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2604..3043
FT /note="Condensation (C) domain"
FT /evidence="ECO:0000255"
FT REGION 3072..3467
FT /note="Adenylation (A) (KR) domain"
FT /evidence="ECO:0000255"
FT REGION 3783..3932
FT /note="Reductase (RED) domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 2511..2546
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2561..2580
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 2439
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3630
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 4023 AA; 438325 MW; 5CF489F95F2CF7D0 CRC64;
MSHSDQDERI AVIGTGCRFP GGCDSPSKLW DLLKAPRDVL REIPRERFDA NAWYHPDNKH
HGTSNVRSAY LLDQDPAAFD NEFFNIQSSE AEAVDPQQRI LLETVYDSLC EAGCTIEGLR
GSNTAVYVGL MCDDWSAIVT KDTEVFPQYA ATGTSRSVMS NRVSYFFDWH GPSMTIDTAC
SSSLVAVHQA IHTLRSGESN VAIAAGANLI LSPDMFIAES NLSMLSAGGR SRMWDRDVDG
YARGEGIAAV VLKRLSDAVR DNDQIECVIR ATSVNQDGKT AGLTMPSGTA QAALIRSTYA
RAGLDISNPR DRPQFFHAHG TGTAAGDPQE ARAIHEAFYS GTARNTDKLY VGSVKTVIGH
TEGTAGLASL ISTSLAMRHK IIPPNMHFNN LNPRLKPYYR NLEVPTKAYP WPEPAPGHPR
RASVNSFGFG GTNAHAIIEE YLPSQTRDLA EHTTAVSLLT PLVFSASSEI SLRSLLASYS
AYLKENLTIS LQSLAYTLQA RRSTMPHRVA ITCNTTSELI SAIDGIISGQ ENSTIAVRHL
SKPTPKVLAV FTGQGAQWAR MGAKLVETSP FVSKRLKELD EALATSAAGN SPQWTLSEMI
LAGPALSRVA EAAISQPLCT AVQIVLVDLL RQAGVRIDAV VGHSSGEIGA AYASGLYTAR
DAIRAAYYRG LYSSLAKSPN GGKGSMMAVS TTHQDAIEFC ELETFEGRLQ VAAVNSFDSI
TLSGDADAVA EACEVYQDEG AFARQLKVDT AYHSSHVLPC SKPYLEAMTS AGREALPKAP
SDALPWPTWY SSVRDGQEMT REDVQPQYWV DNMANPVLFS TAVEAACSDK GLFDLIIEVG
PHPALQKPCL DTVEETAGAR PPYVGLLGRG KDDVSAFSKA LGFIWTQLGP QSVAFDNVER
AASEPPVVPR ELLKDLPQYP FDHSSKFLSL SRVSGFYNRS QMATHPLLGK RCYDRETNLC
IQWRNILSLK EVPWLTGHQI QGLTVFPAAG FVSMAIEAIV ALAKDSTIGL LSLENVNIGR
AMAFQDDSSR VEVLFDMRII AQTPHEIAAE WASYSGDPHD IKTVLTLNAS GVVRATLAEN
NASAEPDVLP ALDVIDNNDL SPVDTERFYK FLRKLGYNYS WPFYGTKSIQ RKAGFSTGML
EDQSGDEWQD QLLVHPGMID TALQTAFAAF CCPGDERLWS LHVPTRFKSL VINPFFTARG
IGKQRMLKFV STAAAVKQGK IAAELYLQSE HEGQTHTFLQ AEGLEIVPLA AAVPDNDTVL
FSRFDYKLAC ADGETAAILD TPLSQDAIDD VINAERVAFY HLYNVVKSIT PGEEASALPH
YQQFLSWARN VVENVLRGDN KYVPASAAQD SASDIASLLT GLPFRFDKNG EVSLAEAIGK
NLISAIRTSS TVFQAEDRNL PAELYEKAIG FDTGNQCLAN MIASISHRYP RMNILEVGSQ
VGSSTEAILS QLDTAFDTYT YTNISDDSFG LAEEHFTAYG DRINFKTLDI TQSPTSQGFA
LGEYDLVVAS NVISSGSDMT ESLTNLRALL KPGGFAVILE PVDNDCLRLG LALGCMPDRS
PPLGLPQWNS LLSETGFSGT DTISPRSHGA VPGVVFCTQA IDDRIKMLRS PLSNISCLPG
LEAPELAIVG RGQSSELQNL CGELSDLLSS AFPKVTFVDS VEQVTAETIP TTSAVIMLAE
LGESPWASLN PVKLEGIKNI YRQARNLLWV TSGADSKDPY SNISLGIGRA MQFEYPHLSI
QALDVDTISE NTAKIIAEHL LRLGTLSTWK EDPEQPTMLW SMEPEVWIKN DMPIIPRLCP
YTPGNDRYNT TRRTVRNQVI PRDTHLALTN DNGAWEVQVT SPLHQAPKIP YATDTKQVRV
TDVLLSTLGI IPGTMLMLCT GQDTSTGEAL LALSPIAETL VQVPRSWTTG IDNAEPRDAL
GAVAANIVAK LMAKSAFRGD VLIVHDPHPA VAHELAIIAN KGAFTIHFTT ASAQVSIEQG
WHHIGSRFSA SKVKSLLPIN ANKLLDLSKS SADGISAHIL SSLPRGCRVV DMSHIMGNTT
ELQSWVSEDE VATVLQESVT EVLRSDRYTN LVNNVPLVSL ESISEPTHHA SFAIADCSVP
AVTARVRAVD DGIIFRGDNT YLLVGLTGEI GRSLCKWMAE RGARHIVLTS RTPKEDVVFS
SAMKALGAVV KYLPMDVRSR DSIHACYAMI QNTMPPVAGV ANGAMIIHDM VFDNMSFEVM
DKVLAPKVVG SQLLDELFYD TPLDFFIFFS SMTAVMGNSG QANYLAGNMY MNALAAQRKE
RGVAGSSINI SSVIGVGYVE RSDQLDEEYF LNMGYRPMSE QDLQVSFAEA IVLGKPGSSE
IAELSTGINS TLNGQSIGKW LQDIKFSHMM MHESNDNAGM GPGASAAPLK VQLSEAKSKE
DIISIIKEVF LARLRRILSI PADKNINEDV TLVEQGVDSL MAVEVRSFFN KELDVDIPVL
KILGDISING IIKQVVELLP AAVYDLPEET PQTLSKNPAP TPVKAPVSAP STPAAASQPV
LTDSTASSSR DSDDDQASSN STSYETSKDA SREDSEVDET PLESPVNTPN VMSKPSASSQ
LLEKKQLLEV DALIASSRPE TLAPMSHGQE GFWFLQDYLP DKTVFNTSVM LKLEGEISVE
TLSQALQMVA RRHEILRTRF FSADDDGEQK VMQAIAANSS LELETKQITS GNEAQVEFTR
FNKHVFDLAN GEAARVLLLS LSKTEHFLMA GMHHIYLDGY SFSIFFNDLN TAYTSKRLPP
LPSNSQYRSF VEQERERYES GEFDETIAHY RETLPKDLAP IELLPFARGT TRREVNNYDQ
TESKMRIDRP LADKIRQLAR NNRSTSFHVF LAAFQALLFQ LLPESDDLII GMGDANRDDK
KYLNSIGYFF NLLPLHFSRF KSGTKIADLV QDSRSAVREA LERPHVPLSI LLDELDVPRS
NKHTPLFQVC IDHRQVLQEQ SNWGGCRVSD EQWHDAGTGF DISLQITEFN TDASLSLRLQ
KPMYTEEHTN MLLRSFVAVL EHMADVPTDN MVEDIPSWSE LDIQKALTVG KGREFHSRWD
SNPPTVMHRI HEMITVHGST TALKDGHGST LSYEQMGRRI AAISAALIEK GIARGDVIGV
FQEPSVDWIC SMMAIFNIGA TYMALDQRLT LPRLATIVQT AKPAAILTDS FTSSQVTDIG
ASAITTVLVS HLASSVNTKP INAARAEDVA VVLFTSGSTG VPKGMRMTHA NLVFSTDSIS
GAFNVTQESM VLQQSPFSFD PSLCQTLVAL TNGAALYVVP SRSRGDPMAV TKIMAEEKVT
FTVGTPSEYA MLLEYGADNI RQCHAWKCAA WGGEQMPHGL AKQLAAANLP GLKAHNVYGP
SETTMLSHFH LVNPAEIEGN GYIPVGAGFD GYKYCIVDHQ MRVQPIGVPG EIIIGGPAVV
AGYLNNQQLT DTKFLADSFF GTNGKVYRSG DLGRMLEDGT LVVEGRLDGD DLIKLRGFRI
ELEEIEKAIV KQADGTLGDA IVSLRGEGDA QFLAAHVTLS ADLSPPAKQK LISALQRLPL
SSYMIPSVFG VIKAIPKTAH DKVDRKAAKE LPLPSADDEN SLAVHGIDGG DDSVLSGTER
QLGTLWRQVI PVYVGSLAST SDFFLAGGNS LLLVKLQALL RTEFGATPKL MDLMGASNLA
AMADAVQKEV DSSLTRDGID WDLETRPPVA LQHKLSGFIS SARTNTTRPD ASRFNVLLTG
ATGQLGRHVL SQLVTNGKTS RVICLTRQPD KIEANDKVTT LRGDVSEPNF GLSEQEYQQL
ATETDVIMHC VANRSFWDRY EVLQPVNVSA VKSLVGLIAD SGRIIPLHFM SSGAVSHYYN
LGTSPPRDGS DGYVASKWAA EGFLRRIAAE TSIPIYIHRP SSVDGDALGS PQEREAVTDQ
LMGIVNSMEI QPEFGGVDGT LDIAPVDDMA QSLAELVLKS ITEAAETDGS EKNLIQEFKH
KAALQVYARD FAARLESEGQ HAQFPKMPIL EWFGQAKAAG FSYIIAAQEL VMTSGLDAIT
TRR
