FSQG_ASPFU
ID FSQG_ASPFU Reviewed; 588 AA.
AC Q4WD48;
DT 15-FEB-2017, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=Phenol 2-monooxygenase fsqG {ECO:0000303|PubMed:27065235};
DE EC=1.14.13.- {ECO:0000305|PubMed:27065235};
DE AltName: Full=Fumipyrrole biosynthesis protein F {ECO:0000303|PubMed:25582336};
DE AltName: Full=Fumisoquins biosynthesis protein G {ECO:0000303|PubMed:27065235};
GN Name=fsqG {ECO:0000303|PubMed:27065235};
GN Synonyms=fmpF {ECO:0000303|PubMed:25582336}; ORFNames=AFUA_6G03490;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP FUNCTION, AND INDUCTION.
RX PubMed=25582336; DOI=10.1111/mmi.12926;
RA Macheleidt J., Scherlach K., Neuwirth T., Schmidt-Heck W., Strassburger M.,
RA Spraker J., Baccile J.A., Schroeder F.C., Keller N.P., Hertweck C.,
RA Heinekamp T., Brakhage A.A.;
RT "Transcriptome analysis of cyclic AMP-dependent protein kinase A-regulated
RT genes reveals the production of the novel natural compound fumipyrrole by
RT Aspergillus fumigatus.";
RL Mol. Microbiol. 96:148-162(2015).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27065235; DOI=10.1038/nchembio.2061;
RA Baccile J.A., Spraker J.E., Le H.H., Brandenburger E., Gomez C., Bok J.W.,
RA Macheleidt J., Brakhage A.A., Hoffmeister D., Keller N.P., Schroeder F.C.;
RT "Plant-like biosynthesis of isoquinoline alkaloids in Aspergillus
RT fumigatus.";
RL Nat. Chem. Biol. 12:419-424(2016).
RN [4]
RP FUNCTION.
RX PubMed=30194285; DOI=10.1074/jbc.ra118.004227;
RA Lahham M., Pavkov-Keller T., Fuchs M., Niederhauser J., Chalhoub G.,
RA Daniel B., Kroutil W., Gruber K., Macheroux P.;
RT "Oxidative cyclization of N-methyl-dopa by a fungal flavoenzyme of the
RT amine oxidase family.";
RL J. Biol. Chem. 293:17021-17032(2018).
CC -!- FUNCTION: Phenol 2-monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of the isoquinoline alkaloids fumisoquin A,
CC fumisoquin B and fumisoquin C; as well as small amounts of fumipyrrole
CC as a shunt metabolite (PubMed:25582336, PubMed:27065235). The products
CC of the cluster lead to a brown coloration and are important for growth
CC and conidiation (PubMed:25582336). The nonribosomal peptide synthetase-
CC like protein fsqF, which lacks a canonical condensation domain, is
CC required for addition of a serine-derived dehydroalanine moiety to
CC activated tyrosine but is not essential for the subsequent steps
CC leading to isoquinoline formation (PubMed:27065235). A different
CC enzyme, most likely the ATP-grasp enzyme fsqD, is responsible for
CC activation of tyrosine (Probable). Three additional enzymes encoded by
CC the fsq cluster, the N-methyltransferase fsqC, the phenol 2-
CC monooxygenase fsqG and the FAD-dependent oxidase fsqB, catalyze the
CC formation of the isoquinoline ring system in the fumisoquins
CC (PubMed:27065235, PubMed:30194285). FsqB converts the fspF thiolation
CC domain-bound (2S,4S,5S)-2-amino-6-(3,4-dihydroxyphenyl)-4-hydroxy-5-
CC (methylamino)hexanoyl into isoquinoline (PubMed:27065235,
CC PubMed:30194285). The cyclization most likely proceeds via a two-step
CC mechanism, beginning with FAD-dependent oxidation of the methyl group
CC to an iminium species followed by electrophilic attack on the
CC deprotonated phenol (Probable). {ECO:0000269|PubMed:25582336,
CC ECO:0000269|PubMed:27065235, ECO:0000269|PubMed:30194285,
CC ECO:0000305|PubMed:27065235}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P15245};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:25582336}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P15245}.
CC -!- INDUCTION: Expression is positively regulated by the fumisoquins
CC biosynthesis specific transcription factor fsqA (PubMed:25582336).
CC {ECO:0000269|PubMed:25582336, ECO:0000269|PubMed:27065235}.
CC -!- DISRUPTION PHENOTYPE: Leads to complete abolishment of isoquinoline
CC alkaloid production but accumulates a series of benzyl pyrroles,
CC including fumipyrrole. {ECO:0000269|PubMed:27065235}.
CC -!- SIMILARITY: Belongs to the PheA/TfdB FAD monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; AAHF01000012; EAL85690.1; -; Genomic_DNA.
DR RefSeq; XP_747728.1; XM_742635.1.
DR AlphaFoldDB; Q4WD48; -.
DR SMR; Q4WD48; -.
DR STRING; 746128.CADAFUBP00009214; -.
DR EnsemblFungi; EAL85690; EAL85690; AFUA_6G03490.
DR GeneID; 3505023; -.
DR KEGG; afm:AFUA_6G03490; -.
DR eggNOG; KOG3855; Eukaryota.
DR HOGENOM; CLU_009665_9_2_1; -.
DR InParanoid; Q4WD48; -.
DR OMA; ANWFRNS; -.
DR OrthoDB; 366744at2759; -.
DR Proteomes; UP000002530; Chromosome 6.
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; 3.40.30.20; -; 1.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR012941; Phe_hydrox_C_dim_dom.
DR InterPro; IPR038220; PHOX_C_sf.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR Pfam; PF07976; Phe_hydrox_dim; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
PE 2: Evidence at transcript level;
KW FAD; Flavoprotein; Monooxygenase; Oxidoreductase; Reference proteome.
FT CHAIN 1..588
FT /note="Phenol 2-monooxygenase fsqG"
FT /id="PRO_0000438874"
FT BINDING 9..38
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15245"
FT BINDING 17..18
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15245"
FT BINDING 37..39
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15245"
FT BINDING 45..50
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15245"
FT BINDING 49
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P15245"
FT BINDING 232
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15245"
FT BINDING 232
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P15245"
FT BINDING 289..299
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15245"
FT BINDING 299
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15245"
FT BINDING 309..313
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15245"
SQ SEQUENCE 588 AA; 65844 MW; BEFE9CF8C3077E57 CRC64;
MSNASDHVDV LIIGAGPAGL TTANSFNGSN CRVRLIDWKP APLETGRADG LKSISLEVLD
SFGIGDRVLN DCQPCEEIVL WNPGKDGVIA RTMTIPDKVE ELGQIERVMV ENLYRHKTVQ
VNWNTQPVRL HIAPVTKDEP EAHPLTITVQ NKETLGQETI RAKYVVGADG AHSWLRKYLN
IGFSGDVTDS TWGVMNLVPK TDFPDIRKVF VVHSRAGTVM GVPREDKLVR LYISMDGGNR
HTSIDAKSIT AENLLQAARA ILAPYRLDAA RIPWWSAYCV GQRVADEFAR HNRIFLAGDA
VHTHSPKAGQ GMNTSIQDGY NIGWKLRYCL EQKASPALLS TYQTERRPIA QALIDFDRKY
LESFTRRDIT HQEFLEAYLA GQRFTTGIQI QYPPSLIVTA KHLHAPSHPL ATNLAPGKRL
PDFQMVNQSD AVPIQAYHRF TSDGRFRLLV FPGDISQALA FGRFSRLGDW LTSHLPPSSG
LEIITIHGAR RADVELMDLH PAFRPWSDEE GWNYWTVYAD DDSYHKGHGH VYERCGISKE
DGVLVLLRPD GYISLIASFD ETHELIDFFD GLQSGPRTVP QPERRANL
