VIRI_HYPVG
ID VIRI_HYPVG Reviewed; 510 AA.
AC G9N4A4;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 22-FEB-2012, sequence version 1.
DT 25-MAY-2022, entry version 42.
DE RecName: Full=FAD-linked oxidoreductase virI {ECO:0000303|PubMed:31790246};
DE EC=1.-.-.- {ECO:0000305|PubMed:31790246};
DE AltName: Full=Trichoxide biosynthesis protein virI {ECO:0000303|PubMed:31790246};
DE AltName: Full=Virensol biosynthesis cluster protein I {ECO:0000303|PubMed:31790246};
DE Flags: Precursor;
GN Name=virI {ECO:0000303|PubMed:31790246}; ORFNames=TRIVIDRAFT_68450;
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: FAD-linked oxidoreductase; 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=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q5BEJ5};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:31790246}.
CC -!- PATHWAY: Polyketide biosynthesis. {ECO:0000305|PubMed:31790246}.
CC -!- SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; ABDF02000086; EHK18430.1; -; Genomic_DNA.
DR RefSeq; XP_013952630.1; XM_014097155.1.
DR AlphaFoldDB; G9N4A4; -.
DR SMR; G9N4A4; -.
DR STRING; 413071.G9N4A4; -.
DR EnsemblFungi; EHK18430; EHK18430; TRIVIDRAFT_68450.
DR GeneID; 25797098; -.
DR VEuPathDB; FungiDB:TRIVIDRAFT_68450; -.
DR eggNOG; ENOG502SJ3M; Eukaryota.
DR HOGENOM; CLU_018354_0_1_1; -.
DR InParanoid; G9N4A4; -.
DR OMA; KFRWYNP; -.
DR OrthoDB; 350817at2759; -.
DR Proteomes; UP000007115; Unassembled WGS sequence.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.30.43.10; -; 1.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR012951; BBE.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016167; FAD-bd_PCMH_sub1.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR Pfam; PF08031; BBE; 1.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 3: Inferred from homology;
KW FAD; Flavoprotein; Glycoprotein; Oxidoreductase; Reference proteome;
KW Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..510
FT /note="FAD-linked oxidoreductase virI"
FT /evidence="ECO:0000255"
FT /id="PRO_0000449286"
FT DOMAIN 78..248
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT CARBOHYD 130
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 210
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 352
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 372
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 415
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 510 AA; 55992 MW; D5756FBA2D0349B4 CRC64;
MNFKLRTLLA FSLVLFLGIV SSSPIVPHYL RAIDVSKAVT PKQVENDLGK VLSKGTLIFG
PSNPAFADAT ERWSTHSMPA DIQVVIEVAQ ESDVAKVVKY CHQNNINFLA YTRGHGSTNT
VSKFKGIEIN LSKLTGIAIQ PDKKSALFQG GVYADLIINK LWSQGYIVPT GSNGCVGLFG
PALGGGLGRY QGQYGLISDN FVSLNVVLAN GTSTTVNAIS NSDLFWAMKG AGHNFGIVTS
AYIKIYPRKA KTWHYHNYVW SQDKLEKVFE ALNRFQGKGQ IPALMGVNFG QFSIEPRISE
TEAVIIWSFA YDGPAAAAEK LLAPFNAIFA ISSTKGDVSY SELLVAQQTD INSSSCSSQP
YVGSTTWLQT YNVTSQRAIY DLFNKQIAQN PGLAPGARVF FEGYSTKATQ TIDPNSSSYP
HRDEYLLVFF AVVTPPSLES VGRAWADKTL AIWHASQPGR RPATYVNYAV GNEPLESIYG
YNGQLTKLRA LKSKYDPLNK FRWYNPIVAY
