GSFD_PENAE
ID GSFD_PENAE Reviewed; 378 AA.
AC D7PI18;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=O-methyltransferase gsfD {ECO:0000303|PubMed:20534346};
DE EC=2.1.1.- {ECO:0000305|PubMed:20534346};
DE AltName: Full=Griseofulvin synthesis protein D {ECO:0000303|PubMed:20534346};
GN Name=gsfD {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, 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 desmethyl-dechlorogriseofulvin,
CC desmethyl- dehydrogriseofulvin A and desmethyl-griseofulvin
CC (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; ADI24956.1; -; Genomic_DNA.
DR AlphaFoldDB; D7PI18; -.
DR SMR; D7PI18; -.
DR BioCyc; MetaCyc:MON-19270; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0008171; F:O-methyltransferase activity; IEA:InterPro.
DR GO; GO:0046983; F:protein dimerization 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; IPR012967; Plant_MeTrfase_dimerisation.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF08100; Dimerisation; 1.
DR Pfam; PF00891; Methyltransf_2; 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..378
FT /note="O-methyltransferase gsfD"
FT /id="PRO_0000436723"
FT ACT_SITE 286
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 219..220
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
FT BINDING 244
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 266..267
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
FT BINDING 282
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
SQ SEQUENCE 378 AA; 42330 MW; 71BC81E9E9F3DC1B CRC64;
MSTPEQWIQE FEALCSRASI LFPSGIEDEN IRIRALRIAE KAVHQLHTPM TFAEAQTWAP
LELFGAGVAC EMGIFDVLSK SSVPLSPVDI ATELNTDPAL VARIMRLLDA HYMVDQVTLG
QYAANAITRD YVQPYRKGNV MTQVALMPSY FALPAWLRDN DYKVRPDANH CAWQVGANTT
KTFWEMPRTT QEDDFVTFYP FEAVFSTSNV DDILFVDIGG GLGHQAMRVR SAFPRSRGRI
IVQDLPQVTN KITTASLPDV EIMDHDMADP QPVKGARVYY LRGVLHNHAD HISIKYLSQF
AAAMSPESRL LIHEALATDL NPTKNITRFD LSMLASCGGA QRSEAEQKAL LEKVGLEVSG
VWSTPRDWSI MEARLKRE
