ID   BIK2_GIBF5              Reviewed;         489 AA.
AC   S0E2X6;
DT   08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT   18-SEP-2013, sequence version 1.
DT   03-AUG-2022, entry version 35.
DE   RecName: Full=FAD-dependent monooxygenase bik2 {ECO:0000305};
DE            EC=1.-.-.- {ECO:0000269|PubMed:26382642};
DE   AltName: Full=Bikaverin biosynthesis protein 2 {ECO:0000303|PubMed:19400779};
GN   Name=bik2 {ECO:0000303|PubMed:19400779}; ORFNames=FFUJ_06743;
OS   Gibberella fujikuroi (strain CBS 195.34 / IMI 58289 / NRRL A-6831) (Bakanae
OS   and foot rot disease fungus) (Fusarium fujikuroi).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium;
OC   Fusarium fujikuroi species complex.
OX   NCBI_TaxID=1279085;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=CBS 195.34 / IMI 58289 / NRRL A-6831;
RX   PubMed=23825955; DOI=10.1371/journal.ppat.1003475;
RA   Wiemann P., Sieber C.M.K., von Bargen K.W., Studt L., Niehaus E.-M.,
RA   Espino J.J., Huss K., Michielse C.B., Albermann S., Wagner D.,
RA   Bergner S.V., Connolly L.R., Fischer A., Reuter G., Kleigrewe K., Bald T.,
RA   Wingfield B.D., Ophir R., Freeman S., Hippler M., Smith K.M., Brown D.W.,
RA   Proctor R.H., Muensterkoetter M., Freitag M., Humpf H.-U., Gueldener U.,
RA   Tudzynski B.;
RT   "Deciphering the cryptic genome: genome-wide analyses of the rice pathogen
RT   Fusarium fujikuroi reveal complex regulation of secondary metabolism and
RT   novel metabolites.";
RL   PLoS Pathog. 9:E1003475-E1003475(2013).
RN   [2]
RP   FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=19400779; DOI=10.1111/j.1365-2958.2009.06695.x;
RA   Wiemann P., Willmann A., Straeten M., Kleigrewe K., Beyer M., Humpf H.U.,
RA   Tudzynski B.;
RT   "Biosynthesis of the red pigment bikaverin in Fusarium fujikuroi: genes,
RT   their function and regulation.";
RL   Mol. Microbiol. 72:931-946(2009).
RN   [3]
RP   INDUCTION.
RX   PubMed=20572938; DOI=10.1111/j.1365-2958.2010.07263.x;
RA   Wiemann P., Brown D.W., Kleigrewe K., Bok J.W., Keller N.P., Humpf H.U.,
RA   Tudzynski B.;
RT   "FfVel1 and FfLae1, components of a velvet-like complex in Fusarium
RT   fujikuroi, affect differentiation, secondary metabolism and virulence.";
RL   Mol. Microbiol. 77:972-994(2010).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX   PubMed=26382642; DOI=10.1016/j.fgb.2015.09.006;
RA   Arndt B., Studt L., Wiemann P., Osmanov H., Kleigrewe K., Koehler J.,
RA   Krug I., Tudzynski B., Humpf H.U.;
RT   "Genetic engineering, high resolution mass spectrometry and nuclear
RT   magnetic resonance spectroscopy elucidate the bikaverin biosynthetic
RT   pathway in Fusarium fujikuroi.";
RL   Fungal Genet. Biol. 84:26-36(2015).
CC   -!- FUNCTION: FAD-dependent monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of bikaverin, a red pigment also considered
CC       as a mycotoxin (PubMed:19400779). The first stage is catalyzed by the
CC       polyketide synthase bik1, which catalyzes the formation of the
CC       intermediate SMA76a also knowm as pre-bikaverin (PubMed:19400779). FAD-
CC       dependent monooxygenase bik2 might then be responsible for the
CC       oxidation of pre-bikaverin to oxo-pre-bikaverin which is in turn
CC       methylated by the O-methyltransferase bik3 to me-oxo-pre-bikaverin
CC       (PubMed:26382642). A further cycle of oxydation and methylation by bik2
CC       and bik3 leads to the final product of bikaverin, via a nor-bikaverin
CC       intermediate (PubMed:19400779, PubMed:26382642).
CC       {ECO:0000269|PubMed:19400779, ECO:0000269|PubMed:26382642}.
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:19400779, ECO:0000269|PubMed:26382642}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- INDUCTION: Expression is repressed by glutamine and at alkaline ambient
CC       pH and highly induced under nitrogen starvation and acidic pH
CC       conditions (PubMed:19400779). Expression is also negatively regulated
CC       by vel1 (PubMed:20572938). {ECO:0000269|PubMed:19400779,
CC       ECO:0000269|PubMed:20572938}.
CC   -!- DISRUPTION PHENOTYPE: Impairs the production of bikaverin
CC       (PubMed:19400779). Leads to the accumulation of the intermediate pre-
CC       bikaverin (PubMed:26382642). {ECO:0000269|PubMed:19400779,
CC       ECO:0000269|PubMed:26382642}.
CC   -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC       {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; HF679027; CCT67992.1; -; Genomic_DNA.
DR   AlphaFoldDB; S0E2X6; -.
DR   SMR; S0E2X6; -.
DR   STRING; 5127.CCT67992; -.
DR   EnsemblFungi; CCT67992; CCT67992; FFUJ_06743.
DR   VEuPathDB; FungiDB:FFUJ_06743; -.
DR   HOGENOM; CLU_009665_12_2_1; -.
DR   Proteomes; UP000016800; Chromosome 5.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR   Gene3D; 3.50.50.60; -; 1.
DR   InterPro; IPR002938; FAD-bd.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   Pfam; PF01494; FAD_binding_3; 1.
DR   SUPFAM; SSF51905; SSF51905; 1.
PE   1: Evidence at protein level;
KW   Coiled coil; FAD; Flavoprotein; Membrane; Monooxygenase; Oxidoreductase;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..489
FT                   /note="FAD-dependent monooxygenase bik2"
FT                   /id="PRO_0000436339"
FT   TRANSMEM        7..26
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          448..474
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          427..470
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        448..470
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         38..39
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
FT   BINDING         134
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
FT   BINDING         305
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
FT   BINDING         315..319
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
SQ   SEQUENCE   489 AA;  53075 MW;  3E5FA5C1243A539F CRC64;
     MAEPNQHYEV IIAGGGIAGV TLALMFEKLD ISYFLLEGRD TLESDRGAGI GLQPNGLRIL
     DQLGLVEDIE EATIPLEKWF SYDSEGNLMN DSDAMGQYRD KIGYPVAFIE RRKLLPIMVR
     HIQRTECVKT SARVASIEES EDHVTVTTTD GLSLTADIVV GADGVRSAVR THIDSKLPEP
     LTADDYISVA CSTVYGMSAP TEGIAPGERF AVYRENQTVI GFTGKDGIVF WFVFENLNRN
     VPLSQAPRYT EAEAEALCLS VAHTQVTPKL KFGEIYKNSV VAVKIGVEEG VAKGWHTDRA
     VIVGDAACKT TPAGGQGANQ AIESCAVFVN KLMAARKASQ SGDKLSSDVV KSVLASYAQE
     RAQPATTALE RSQMVGKALL CTPGPATTLV KDMLKLSNED WLLRAFMALS AAPYLEDVEL
     TARGHLYNKA VEEARAEMAR RQRVAKEVKE AEEKESKQAA SIKESEQRNE FVGLRNPVQA
     ATGVVEVGS