GSFC_PENAE
ID GSFC_PENAE Reviewed; 396 AA.
AC D7PI17;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 1.
DT 03-AUG-2022, entry version 39.
DE RecName: Full=O-methyltransferase gsfC {ECO:0000303|PubMed:20534346};
DE EC=2.1.1.- {ECO:0000305|PubMed:20534346};
DE AltName: Full=Griseofulvin synthesis protein C {ECO:0000303|PubMed:20534346};
GN Name=gsfC {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, AND DISRUPTION PHENOTYPE.
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: O-methyltransferase; part of the gene cluster that mediates
CC the 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 -!- 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 D, griseoxanthone C and
CC griseophenone H (PubMed:23978092). {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 class I-like SAM-binding methyltransferase
CC superfamily. Cation-independent O-methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU01020}.
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DR EMBL; GU574478; ADI24955.1; -; Genomic_DNA.
DR AlphaFoldDB; D7PI17; -.
DR SMR; D7PI17; -.
DR BioCyc; MetaCyc:MON-19269; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0008171; F:O-methyltransferase activity; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR016461; COMT-like.
DR InterPro; IPR001077; O_MeTrfase_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00891; Methyltransf_2; 1.
DR PIRSF; PIRSF005739; O-mtase; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51683; SAM_OMT_II; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..396
FT /note="O-methyltransferase gsfC"
FT /id="PRO_0000436722"
FT BINDING 234..235
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
FT BINDING 260
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 284..285
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
FT BINDING 300
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
SQ SEQUENCE 396 AA; 43712 MW; 4B24D29E089EDAFB CRC64;
MTLDQISRIQ ALVAEIADLS QTFEGPSERF MVDGLPFLRK SEELVTLVQS PAEHATSLII
KTMETAVIRT LLSLNVLQTI PTTGSITLQS LAVATETQES LLERLLRVVT KTGFIIRENG
GYSHSHTSLA YAGPLGALFA PCYDEGIRAL VRLPEYLSVK DKEEAKNARY SLFTWNEGQE
GKATFEILST MPARTEGIHT LAMNVQHLRP YTGFFDYSKL VSEDRERPVF VDVGGGNGHV
IKEILQAFPQ IRPEQCVLED RAETLELART TGLLPAGVQL LEHDYLTRQP VSNAKAYHLR
AVAYNLGDAE LVQLLKQIVP VMGADSKVLI AENILFDDNS TVFSTVSDMI MLGIGGKERT
EQNFREVLYE AGLTIEGIHR APGLEYGIME ASLATS
