GSFI_PENAE
ID GSFI_PENAE Reviewed; 533 AA.
AC D7PI14;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 1.
DT 03-AUG-2022, entry version 26.
DE RecName: Full=Halogenase gsfI {ECO:0000303|PubMed:20534346};
DE EC=1.14.14.- {ECO:0000269|PubMed:23978092};
DE AltName: Full=Griseofulvin synthesis protein I {ECO:0000303|PubMed:20534346};
GN Name=gsfI {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], FUNCTION, AND DISRUPTION PHENOTYPE.
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, PATHWAY, 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: Halogenase; part of the gene cluster that mediates the
CC biosynthesis of griseofulvin, an important antifungal drug that has
CC been in use for a long time for treating dermatophyte infections
CC (PubMed:20534346, PubMed:23978092). The first step of the pathway is
CC the formation of the heptaketide backbone by gsfA which is initiated by
CC priming with acetyl-CoA, followed by sequential condensations of 6
CC malonyl-CoA units (PubMed:20534346). O-methylation at 3-OH by gsfB
CC leads to griseophenone D which is further methylated at 9-OH by gsfC to
CC yield griseophenone C (PubMed:23978092). Griseophenone C is then
CC substrate of halogenase gsfI which is responsible for the regio-
CC 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=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P95480};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:P95480};
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 intermediate dechlorogriseofulvin (PubMed:20534346,
CC PubMed:23978092). {ECO:0000269|PubMed:20534346,
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 flavin-dependent halogenase family.
CC {ECO:0000305}.
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DR EMBL; GU574478; ADI24948.1; -; Genomic_DNA.
DR AlphaFoldDB; D7PI14; -.
DR SMR; D7PI14; -.
DR PRIDE; D7PI14; -.
DR BioCyc; MetaCyc:MON-19271; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR006905; Flavin_halogenase.
DR Pfam; PF04820; Trp_halogenase; 2.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Monooxygenase; Oxidoreductase.
FT CHAIN 1..533
FT /note="Halogenase gsfI"
FT /id="PRO_0000436730"
FT BINDING 14..17
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P95480"
FT BINDING 37..48
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P95480"
FT BINDING 331..332
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P95480"
SQ SEQUENCE 533 AA; 58507 MW; 732A51BF6F0BF24D CRC64;
MAIPQSCTVL VAGGGPGGSY TAAALAREGV DVVLLEADCH PRYHIGESLL PSMRYLLRFI
DLEDTFEQHG FQKKLGAFFK LNAKSAGYTD FIRANGPNGY SWNVVRSESD EILFRHATKS
GAKTFENVSL KSVNFEPYEN DKFTSQDKLT NPGRPVSAEW KTKDGCSGTI SFDYLVDATG
RVGILSTKYL KNRKFNESFR NIAMWGYFKG NIPPSPGTDR ENQPISEGMR DGSGWVWMLP
LHNGTVSIGA VVRKDIFQAK KKALPEGTTE AQTLASLVAL CPTISSYLEP AELASGIRQA
ADYSYSANAY AGPNFRIVGD AGCFIDPFFS SGHHLALSSA LAAATSINAC IRGDCNEFDA
SRWFAKKVDE GYTLFLVVVM AALKQIRMQE QPILSDLDEE GFDRAFTILR PVIQGAADKE
TAPKAKGESI TETIDLCLTA LNDLHDTELQ RKLTSIVEAK GTPEQEQLLG KLSPDETAAL
HRMRAMHSIL PMGELEDFEN SNIDGFKARL EKGSLGLRRE RALCRDHAGD LQM
