VIRA_HYPVG
ID VIRA_HYPVG Reviewed; 2381 AA.
AC G9N4B2;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 22-FEB-2012, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=Highly reducing polyketide synthase virA {ECO:0000303|PubMed:31790246};
DE Short=HRPKS virA {ECO:0000303|PubMed:31790246};
DE EC=2.3.1.- {ECO:0000269|PubMed:31790246};
DE AltName: Full=Trichoxide biosynthesis protein virA {ECO:0000303|PubMed:31790246};
DE AltName: Full=Virensol biosynthesis cluster protein A {ECO:0000303|PubMed:31790246};
GN Name=virA {ECO:0000303|PubMed:31790246}; ORFNames=TRIVIDRAFT_47407;
OS Hypocrea virens (strain Gv29-8 / FGSC 10586) (Gliocladium virens)
OS (Trichoderma virens).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Hypocreaceae; Trichoderma.
OX NCBI_TaxID=413071;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Gv29-8 / FGSC 10586;
RX PubMed=21501500; DOI=10.1186/gb-2011-12-4-r40;
RA Kubicek C.P., Herrera-Estrella A., Seidl-Seiboth V., Martinez D.A.,
RA Druzhinina I.S., Thon M., Zeilinger S., Casas-Flores S., Horwitz B.A.,
RA Mukherjee P.K., Mukherjee M., Kredics L., Alcaraz L.D., Aerts A., Antal Z.,
RA Atanasova L., Cervantes-Badillo M.G., Challacombe J., Chertkov O.,
RA McCluskey K., Coulpier F., Deshpande N., von Doehren H., Ebbole D.J.,
RA Esquivel-Naranjo E.U., Fekete E., Flipphi M., Glaser F.,
RA Gomez-Rodriguez E.Y., Gruber S., Han C., Henrissat B., Hermosa R.,
RA Hernandez-Onate M., Karaffa L., Kosti I., Le Crom S., Lindquist E.,
RA Lucas S., Luebeck M., Luebeck P.S., Margeot A., Metz B., Misra M.,
RA Nevalainen H., Omann M., Packer N., Perrone G., Uresti-Rivera E.E.,
RA Salamov A., Schmoll M., Seiboth B., Shapiro H., Sukno S.,
RA Tamayo-Ramos J.A., Tisch D., Wiest A., Wilkinson H.H., Zhang M.,
RA Coutinho P.M., Kenerley C.M., Monte E., Baker S.E., Grigoriev I.V.;
RT "Comparative genome sequence analysis underscores mycoparasitism as the
RT ancestral life style of Trichoderma.";
RL Genome Biol. 12:R40.1-R40.15(2011).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, DOMAIN, AND PATHWAY.
RX PubMed=31790246; DOI=10.1021/jacs.9b09669;
RA Liu L., Tang M.C., Tang Y.;
RT "Fungal highly reducing polyketide synthases biosynthesize salicylaldehydes
RT that are precursors to epoxycyclohexenol natural products.";
RL J. Am. Chem. Soc. 141:19538-19541(2019).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of virensols and trichoxide, fungal
CC natural products that contain or are derived from a salicylaldehyde
CC core (PubMed:31790246). The pathway begins with the synthesis of the
CC reduced chain in virensol C by the highly reducing polyketide synthase
CC virA via condensation of one acetate and 8 malonate units
CC (PubMed:31790246). VirA has interesting programming rules since the
CC first 2 ketides are fully reduced, the 3 following ketides undergo
CC beta-dehydration, and the last 3 ketides are only reduced to beta-
CC hydroxys to yield the trihydroxy portion (PubMed:31790246). The
CC production of aldehyde virensol C by virA alone is surprising, since
CC virA does not contain a reductase (R) domain that is typically
CC associated with reductive product release in HRPKS (PubMed:31790246).
CC The cupin-domain enzyme virC is involved in enhancing virA product
CC turnover (PubMed:31790246). The short-chain dehydrogenase virB then
CC oxidizes the C-7 alcohol of virensol C to a ketone, yielding virensol D
CC (PubMed:31790246). Virensol D is further transformed to salicylaldehyde
CC 5-deoxyaurocitrin by the short-chain dehydrogenase virD
CC (PubMed:31790246). VirD catalyzes the dehydrogenation of C-3 to form
CC the beta-ketone aldehyde, which is followed by the generation of the
CC nucleophilic C-2 that is required for the intramolecular aldol
CC condensation between C-2 and C-7, itself followed by dehydration and
CC aromatization which leads to salicylaldehyde 5-deoxyaurocitrin
CC (PubMed:31790246). While the dehydrogenation of virensol D is
CC definitely catalyzed by virD, the aldol condensation and dehydration
CC may be uncatalyzed or assisted by virD (PubMed:31790246). The short
CC chain dehydrogenase virG then converts salicylaldehyde 5-
CC deoxyaurocitrin into virensol B which is further hydroxylated by the
CC cytochrome P450 monooxygenase virE to yield the hydroquinone virensol A
CC (PubMed:31790246). VirI then may oxidize virensol A to form the
CC quinone, while virH performs the epoxidation (PubMed:31790246).
CC Finally, the two remaining short-chain dehydrogenases, virK and virL,
CC are probably responsible for reducing the ketones to the corresponding
CC alcohols to furnish the epoxycyclohexanol structure in trichoxide
CC (PubMed:31790246). {ECO:0000269|PubMed:31790246}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:31790246}.
CC -!- DOMAIN: Multidomain protein; including a ketosynthase (KS) that
CC catalyzes repeated decarboxylative condensation to elongate the
CC polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects
CC and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain
CC that reduces hydroxyl groups to enoyl groups; an enoyl reductase (ER)
CC domain that reduces enoyl groups to alkyl group; a ketoreductase (KR)
CC domain that catalyzes beta-ketoreduction steps; and an acyl-carrier
CC protein (ACP) that serves as the tether of the growing and completed
CC polyketide via its phosphopantetheinyl arm.
CC {ECO:0000305|PubMed:31790246}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of trichoxide, virensol
CC A, virensol B and salicylaldehyde 5-deoxyaurocitrin.
CC {ECO:0000269|PubMed:31790246}.
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DR EMBL; ABDF02000086; EHK18438.1; -; Genomic_DNA.
DR RefSeq; XP_013952638.1; XM_014097163.1.
DR AlphaFoldDB; G9N4B2; -.
DR SMR; G9N4B2; -.
DR STRING; 413071.G9N4B2; -.
DR EnsemblFungi; EHK18438; EHK18438; TRIVIDRAFT_47407.
DR GeneID; 25794654; -.
DR VEuPathDB; FungiDB:TRIVIDRAFT_47407; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_31_4_1; -.
DR InParanoid; G9N4B2; -.
DR OMA; KDVQHYT; -.
DR OrthoDB; 19161at2759; -.
DR Proteomes; UP000007115; Unassembled WGS sequence.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 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; IPR013149; ADH-like_C.
DR InterPro; IPR011032; GroES-like_sf.
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; 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; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00107; ADH_zinc_N; 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; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Multifunctional enzyme; NADP; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..2381
FT /note="Highly reducing polyketide synthase virA"
FT /id="PRO_0000449279"
FT DOMAIN 2297..2375
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:31790246"
FT REGION 6..423
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31790246"
FT REGION 535..851
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31790246"
FT REGION 920..1232
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31790246"
FT REGION 1639..1956
FT /note="Enoyl reductase (ER) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31790246"
FT REGION 1981..2159
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31790246"
FT ACT_SITE 629
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 952
FT /note="For beta-hydroxyacyl dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2334
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2381 AA; 258862 MW; F137682ABA672A0F CRC64;
MDALHLACHL PGGITSPSGL WDYVYNKKSA QCTVPLDRYN IEGFYHKDGS RAGVMSVDGG
YFIQEDVRKF DPSFFGINNL EASYMDPQQR KLLEVVYECF ENAGLSMEDV SGSNTAVFVG
NFTVDYSVMQ SRDTDYVHRL AATGGGTSIM SNRISHVFNL HGPSFTLDTA CSSTIYALHQ
AVNAIKNGDC DAAIVAGANL ITSPEQHFGT AKGGFLSPTS ACHTFDTSAD GYARAEALNA
IYITRLSSAM KSDRKIHAVI RGTAINANGK TPGITLPDAK MQAAVIRKAY QNAGLSFADT
DYVECHGTGT PVGDPIEVDG IAACFAGREG EPLRIGSVKT NMGHSEAASG LTSIIKVALA
FEHGMIPPTY GVKNLNPKLK LKERNMKVLT EVEAWPRALR RAGVNSFGYG GANGHVILES
IDSYFVGSLV SSPITRALSN PYESEKDYVV VIPFSASSGK SLEARRKQAI ETVEKTEASA
LKPLAAAMSK RQTKMRLRDY VLASASSNSQ PSLIDMTDVG DKASPGTQPL PFAFVFTGQG
AQYANMAKEL VEQDFGFLTS IRDLDEVLQS LPAEYKPSWT LEQTILDKPA TSKINDVTRS
QPICTAVQVS LVNMLQSWGV SPSAVIGHSS GEIAAAYGSG LLTASEAILA AYFRGFAVGQ
LQSRGAMMAV GITPDGAIAL IEQLGLKEVR VACVNAPESV TLSGAVKDID SLQAKLQKEK
KFARKLETGG RAYHSHMMAE IGDLYESLVT PYITVKKVAE MEVKMFSTVG HSIDALGTVD
LSTEMASYFR KNLEQPVQFS AGLANMITSN KYHLIEIGPH SALKGPIQQI RTSAKRDKEG
VPYSPTLVRK ENSYVCLKKL AGTLFSYGHS LDWYAVNNVP RYHALPTPPL ASYPWDYSKP
LPWHEPRASV EHRLRKHVRH ELLGTRATAG NGIEWCWRNI PRMSEMPWLR DHKLGESQVV
LPGAAYMAMA IEAFSQVHEI KGKLIAGEPF SFEFENVNIS AAFVVPDEND AEADKTELHT
LMSPRKISTA NISGNWHEFS ISSWVSGIAT LHCMGSIRVM ESTLKPKDGS VMISGNGHEV
WGMSRWYAKA KEEGLNFGPT FQSLTSLHTD GNRTSTDSIA TTLLDPPSAA ATGMFYAVHP
ITIDACFQAT IMGGTAGNIN TLRAYVPVFV SSCSIQIPRG GSASLGEEEV RIHSRMEKTG
FSTRAVSFTL RLPDGTPVID MPHLRMNEYT GKAPVEPETS IYLQRQPCLR VQWKPDVLRL
RPGSDGAIRE YIASFAAQQS DDLKDNGALV VFAALLDLFG HKVPRMSVLE LGQESQWTPK
DCQSILGKGT AFPRFRLWND GKLGDNSKII VDNAKNSDSY DVVLIPHLSV SNKIWAEAAD
AIISLISDDG IIITRRSKDV VSALKTSGFV VLELPNETLV AVRSPKQTGL ENKEVVIVKP
NEASPSINSL ATAVATHLKN AGVVQLRTVT IDSIETVNLN SQVVCVSLLE MEHEFLATIN
SEDMDRFRKI TDNVGDLLWL TGANMLSTPN PDLTLSSGLS RALMLEQPAL RYAILDVGAD
ISKPNSMELI CNSVSASLVF RHATDDKEFI QKDGIVYISR FVPDVELNAL FRHRMTPDSM
KLVPLREVGP AKLSIGQVGM TDTIHFQQIS ERKTTPPAGF VDVDLRAIGL NAKDVYALNG
RAETRSATTA LDFGGVISAV GPGIEHLKVG DRVAGFIPNH FGTTERVTVQ AVHKMLPEEE
FTVLPTLLTV YCTALVALRD RAHLRAGESI LIHSGAGAFG LAAITMAKYM GATVFATVGS
HSKREYLIKE MGVPTENIFN SRSASFMEDI LAATGGRGVN VIVNSLVGDL MHASWSCIAP
FGRFVEIGKR ELIDAGKLDM RVFLKNATFT AFDLSEFFYA EDSYYQDIVY GYTAEVIEMY
RAGIIKASPI ATFDVAEIGQ AYRYFGNKDR VGKVVVSMEN SRSLIQVVPA SYQSVFHPEK
TYLLVGCLGG LGRSLSRWMM SRGARKFCFL GRSGCDKPSA AELVNRLRDA GASVTVVRGD
VSNEDQVREA VAACSKKGPI GGVVQAAMGL SEALFSVMTN KAWHTGIQPK WKGSWNLHHA
LEGHDADLDF FLLTSSISGS CGTATESNYC SANGFLDSFA RWRRSQGKPA VSVGLGMISE
VGYLHENPDI EAMLLRKGIQ PLNEDEFLQV LDYGISGPGS DSEFGRGVSM TSESAHILTG
LESYGVRKLM AQGFEVNNGV MDESRTSILA ASLLSEKDAK EEEKGADVGQ LLAAAEWVKD
VPANALSMLI PEASAPTMLD AILRLTKKRF SNLILMQLDA VDDSAPLPSF GVDSMLAAEF
RTWFFNTFKI DVPFLDIVSP QKSLHTLAEF IEEKLVASWA S
