VIRE_HYPVG
ID VIRE_HYPVG Reviewed; 551 AA.
AC G9N4A8;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 22-FEB-2012, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=Cytochrome P450 monooxygenase virE {ECO:0000303|PubMed:31790246};
DE EC=1.-.-.- {ECO:0000269|PubMed:31790246};
DE AltName: Full=Trichoxide biosynthesis protein virE {ECO:0000303|PubMed:31790246};
DE AltName: Full=Virensol biosynthesis cluster protein E {ECO:0000303|PubMed:31790246};
DE Flags: Precursor;
GN Name=virE {ECO:0000303|PubMed:31790246}; ORFNames=TRIVIDRAFT_47601;
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, CATALYTIC ACTIVITY, 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: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of virensols and trichoxide, fungal natural
CC products that contain or are derived from a salicylaldehyde core
CC (PubMed:31790246). The pathway begins with the synthesis of the reduced
CC chain in virensol C by the highly reducing polyketide synthase virA via
CC condensation of one acetate and 8 malonate units (PubMed:31790246).
CC VirA has interesting programming rules since the first 2 ketides are
CC fully reduced, the 3 following ketides undergo beta-dehydration, and
CC the last 3 ketides are only reduced to beta-hydroxys to yield the
CC trihydroxy portion (PubMed:31790246). The production of aldehyde
CC virensol C by virA alone is surprising, since virA does not contain a
CC reductase (R) domain that is typically associated with reductive
CC product release in HRPKS (PubMed:31790246). The cupin-domain enzyme
CC virC is involved in enhancing virA product turnover (PubMed:31790246).
CC The short-chain dehydrogenase virB then oxidizes the C-7 alcohol of
CC virensol C to a ketone, yielding virensol D (PubMed:31790246). Virensol
CC D is further transformed to salicylaldehyde 5-deoxyaurocitrin by the
CC short-chain dehydrogenase virD (PubMed:31790246). VirD catalyzes the
CC dehydrogenation of C-3 to form the beta-ketone aldehyde, which is
CC followed by the generation of the nucleophilic C-2 that is required for
CC the intramolecular aldol condensation between C-2 and C-7, itself
CC followed by dehydration and aromatization which leads to
CC salicylaldehyde 5-deoxyaurocitrin (PubMed:31790246). While the
CC dehydrogenation of virensol D is definitely catalyzed by virD, the
CC aldol condensation and dehydration may be uncatalyzed or assisted by
CC virD (PubMed:31790246). The short chain dehydrogenase virG then
CC converts salicylaldehyde 5-deoxyaurocitrin into virensol B which is
CC further hydroxylated by the cytochrome P450 monooxygenase virE to yield
CC the hydroquinone virensol A (PubMed:31790246). VirI then may oxidize
CC virensol A to form the quinone, while virH performs the epoxidation
CC (PubMed:31790246). Finally, the two remaining short-chain
CC dehydrogenases, virK and virL, are probably responsible for reducing
CC the ketones to the corresponding alcohols to furnish the
CC epoxycyclohexanol structure in trichoxide (PubMed:31790246).
CC {ECO:0000269|PubMed:31790246}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:31790246}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; ABDF02000086; EHK18434.1; -; Genomic_DNA.
DR RefSeq; XP_013952634.1; XM_014097159.1.
DR AlphaFoldDB; G9N4A8; -.
DR SMR; G9N4A8; -.
DR STRING; 413071.G9N4A8; -.
DR EnsemblFungi; EHK18434; EHK18434; TRIVIDRAFT_47601.
DR GeneID; 25794681; -.
DR VEuPathDB; FungiDB:TRIVIDRAFT_47601; -.
DR eggNOG; KOG0156; Eukaryota.
DR HOGENOM; CLU_001570_2_1_1; -.
DR InParanoid; G9N4A8; -.
DR OMA; STFMQWI; -.
DR OrthoDB; 702827at2759; -.
DR Proteomes; UP000007115; Unassembled WGS sequence.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..551
FT /note="Cytochrome P450 monooxygenase virE"
FT /evidence="ECO:0000255"
FT /id="PRO_5003524545"
FT BINDING 439
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CARBOHYD 392
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 551 AA; 62674 MW; 91DB01AF1E6EEEE6 CRC64;
MPKPWVVFGL GTLVLFLWRL NKIGRRPKNY PPGPPTLPLI GNLHLMPKKN AHLQFQRWAE
EYGPVYSLML GTKVAIVLSS DVAVKDLLDK RSSIYSGRPE LYMGQEIMSG GNRPLFMGIN
SVWRRVRKLA HGLLNVKVSR TYVPYQDLES RDMLMGLLES PKDFLNHIRR YTTSLTTQMA
FGYRTPSSDD KGLLEMFENF DELSRLTGSQ SAAILDLYPI ARILPDFLLP ARRLGREYYE
REKKLFMKHF LNARQQLNSG TSKPCCAIDL LRAQKEYGFS DEFGCYLSGS LLQAGSETTA
IILTGFFQAM LVFPEVSKEA QEEIDRVCGD RLPDLNDYPN LPYIRACLKE SLRWMPATAL
GVPHAVIQDD SYLGYHIPKD AGLILNVWAI HNDSKRHPDP RRYNPARWAG DNQNSAQAAV
NPDPTKRDHF VFGAGRRLCQ GMHIADRSLF LAISRTLWAF DLKRPVDKET GHEIIPDVDN
IKDGLFISPM PFAADIVPRS ESRAAAVRQE WENVAGLLDD DMQWKTVPEG LKWKDYEPLD
DENEDLLESL S
