ID   VIRC_HYPVG              Reviewed;         194 AA.
AC   G9N4B0;
DT   22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT   22-FEB-2012, sequence version 1.
DT   25-MAY-2022, entry version 37.
DE   RecName: Full=Cupin-domain-containing oxidoreductase virC {ECO:0000303|PubMed:31790246};
DE            EC=1.-.-.- {ECO:0000305|PubMed:31790246};
DE   AltName: Full=Trichoxide biosynthesis protein virC {ECO:0000303|PubMed:31790246};
DE   AltName: Full=Virensol biosynthesis cluster protein C {ECO:0000303|PubMed:31790246};
GN   Name=virC {ECO:0000303|PubMed:31790246}; ORFNames=TRIVIDRAFT_194203;
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, 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: Cupin-domain-containing oxidoreductase; part of the gene
CC       cluster that mediates the biosynthesis of virensols and trichoxide,
CC       fungal natural products that contain or are derived from a
CC       salicylaldehyde core (PubMed:31790246). The pathway begins with the
CC       synthesis of the reduced chain in virensol C by the highly reducing
CC       polyketide synthase virA via condensation of one acetate and 8 malonate
CC       units (PubMed:31790246). VirA has interesting programming rules since
CC       the 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   -!- SIMILARITY: Belongs to the virC family. {ECO:0000305}.
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DR   EMBL; ABDF02000086; EHK18436.1; -; Genomic_DNA.
DR   RefSeq; XP_013952636.1; XM_014097161.1.
DR   AlphaFoldDB; G9N4B0; -.
DR   SMR; G9N4B0; -.
DR   STRING; 413071.G9N4B0; -.
DR   EnsemblFungi; EHK18436; EHK18436; TRIVIDRAFT_194203.
DR   GeneID; 25789802; -.
DR   VEuPathDB; FungiDB:TRIVIDRAFT_194203; -.
DR   eggNOG; ENOG502SKGF; Eukaryota.
DR   HOGENOM; CLU_096188_0_2_1; -.
DR   InParanoid; G9N4B0; -.
DR   OMA; SIVRMID; -.
DR   OrthoDB; 1417496at2759; -.
DR   Proteomes; UP000007115; Unassembled WGS sequence.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   Gene3D; 2.60.120.10; -; 1.
DR   InterPro; IPR013096; Cupin_2.
DR   InterPro; IPR014710; RmlC-like_jellyroll.
DR   InterPro; IPR011051; RmlC_Cupin_sf.
DR   Pfam; PF07883; Cupin_2; 1.
DR   SUPFAM; SSF51182; SSF51182; 1.
PE   3: Inferred from homology;
KW   Oxidoreductase; Reference proteome.
FT   CHAIN           1..194
FT                   /note="Cupin-domain-containing oxidoreductase virC"
FT                   /id="PRO_0000449289"
FT   REGION          106..175
FT                   /note="Cupin-like domain"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   194 AA;  21577 MW;  C4BB6CBC12B58B47 CRC64;
     MADQQQNPQE SELLLTSAGY VSTFPAPGLR RTVRHITGHN AEGKGVFIQT DCGDHHRIIG
     NEQALANIIY STKETPVEMN GDVDLKYAKE NEPPLHIHNG SVCRMIDFAP NVISPMHRAV
     SLDYGIVIEG EFKLILDSGE SRIMRQGDVS VQRASAHQWH NITGNGTLPG RMMWVLLDCK
     PIVINDIDFM ECSQ