GSFF_PENAE
ID GSFF_PENAE Reviewed; 504 AA.
AC D7PI20;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 26-NOV-2014, sequence version 2.
DT 03-AUG-2022, entry version 29.
DE RecName: Full=Cytochrome P450 monooxygenase gsfF {ECO:0000303|PubMed:20534346};
DE EC=1.-.-.- {ECO:0000269|PubMed:23978092};
DE AltName: Full=Griseofulvin synthesis protein F {ECO:0000303|PubMed:20534346};
DE Flags: Precursor;
GN Name=gsfF {ECO:0000303|PubMed:20534346};
OS Penicillium aethiopicum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=36650;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=IBT 5753;
RX PubMed=20534346; DOI=10.1016/j.chembiol.2010.03.015;
RA Chooi Y.H., Cacho R., Tang Y.;
RT "Identification of the viridicatumtoxin and griseofulvin gene clusters from
RT Penicillium aethiopicum.";
RL Chem. Biol. 17:483-494(2010).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=13577889; DOI=10.1038/182476a0;
RA Gentles J.C.;
RT "Experimental ringworm in guinea pigs: oral treatment with griseofulvin.";
RL Nature 182:476-477(1958).
RN [3]
RP BIOTECHNOLOGY.
RX PubMed=4583105; DOI=10.1038/244292a0;
RA Gull K., Trinci A.P.;
RT "Griseofulvin inhibits fungal mitosis.";
RL Nature 244:292-294(1973).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND CATALYTIC ACTIVITY.
RX PubMed=23978092; DOI=10.1021/cb400541z;
RA Cacho R.A., Chooi Y.H., Zhou H., Tang Y.;
RT "Complexity generation in fungal polyketide biosynthesis: a spirocycle-
RT forming P450 in the concise pathway to the antifungal drug griseofulvin.";
RL ACS Chem. Biol. 8:2322-2330(2013).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of griseofulvin, an important antifungal drug
CC that has been in use for a long time for treating dermatophyte
CC infections (PubMed:20534346, PubMed:23978092). The first step of the
CC pathway is the formation of the heptaketide backbone by gsfA which is
CC initiated by priming with acetyl-CoA, followed by sequential
CC condensations of 6 malonyl-CoA units (PubMed:20534346). O-methylation
CC at 3-OH by gsfB leads to griseophenone D which is further methylated at
CC 9-OH by gsfC to yield griseophenone C (PubMed:23978092). Griseophenone
CC C is then substrate of halogenase gsfI which is responsible for the
CC regio-specific chlorination at the C13 position to form griseophenone B
CC (PubMed:23978092). The cytochrome P450 gsfF catalyzes the coupling of
CC orcinol and phloroglucinol rings in griseophenone B to form desmethyl-
CC dehydrogriseofulvin A which is further methylated at 5-OH by gsfD to
CC yield dehydrogriseofulvin (PubMed:23978092). Finally, gsfE performs
CC stereospecific reduction of enone 18 of dehydrogriseofulvin to afford
CC the final product griseofulvin (PubMed:23978092).
CC {ECO:0000269|PubMed:20534346, ECO:0000269|PubMed:23978092}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:20534346, ECO:0000269|PubMed:23978092}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of griseofulvin, but
CC accumulates the intermediates griseophenone C, monochlorinated
CC griseophenone G and dichlorinated griseophenone G (PubMed:23978092).
CC {ECO:0000269|PubMed:23978092}.
CC -!- BIOTECHNOLOGY: Griseofulvin is a spirocyclic fungal natural product
CC used in treatment of fungal dermatophytes (PubMed:13577889,
CC PubMed:4583105). {ECO:0000269|PubMed:13577889,
CC ECO:0000269|PubMed:4583105}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; GU574478; ADI24958.2; -; Genomic_DNA.
DR AlphaFoldDB; D7PI20; -.
DR SMR; D7PI20; -.
DR BioCyc; MetaCyc:MON-19272; -.
DR UniPathway; UPA00213; -.
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 GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
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.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Signal.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..504
FT /note="Cytochrome P450 monooxygenase gsfF"
FT /evidence="ECO:0000255"
FT /id="PRO_0000436726"
FT BINDING 450
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 97
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 150
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 504 AA; 56439 MW; 69B20F24D94F1B71 CRC64;
MTVLFILSAG LVAVFGYLVS WFIYCRTLHP LSKVPGPFWP SVTRLWLTYA VSRGELDVVQ
RDLHRRYGPL VRIAPDEIAC ADPEAIRKIY STTSPLNKSD FYHIWDVGAF SKYPNAFAIV
DENMHFERRR IVSSVYSMST VLTLEPYIDN CSRLFVKRMT ERTVPHEAID LGDWFLWYAY
DVIGELFFGH SLGFIENRGD EGGFLASLEV MLPVLTIAAA SSPLVRGLIM GLFTLSSTAR
KGLKGMNHII ETARASVDKR ASAVAEPGKG ERKDLLHNLL NIVSSKGDKL DFGIEDVKNE
AFAALTAGAD ATMIELQAIF YYLVKDRSVY EELRKEVDQA VETGKLSEFP SYSEVVQLPL
LKATIKEALR LHPAVGFTMP RVVGQAGIEL LGMYIPPGWK VGMNAAVVGR DEGVYGTDAN
TFRPERWIER TDSDMDRCNN LVFGAGTRTC IGKQIALSEI YKMVPLLIRK FDFALVDPSK
SWTTHDYFFN KQSGVQVKVT VRGL
