GSFB_PENAE
ID GSFB_PENAE Reviewed; 419 AA.
AC D7PI16;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 1.
DT 03-AUG-2022, entry version 33.
DE RecName: Full=O-methyltransferase gsfB {ECO:0000303|PubMed:20534346};
DE EC=2.1.1.- {ECO:0000269|PubMed:23978092};
DE AltName: Full=Griseofulvin synthesis protein B {ECO:0000303|PubMed:20534346};
GN Name=gsfB {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, 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: 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 norlichexanthone, griseophenone E,
CC griseophenone F and desmethyl-dehydrogriseofulvin B (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 class I-like SAM-binding methyltransferase
CC superfamily. Cation-independent O-methyltransferase family.
CC {ECO:0000305}.
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DR EMBL; GU574478; ADI24954.1; -; Genomic_DNA.
DR AlphaFoldDB; D7PI16; -.
DR SMR; D7PI16; -.
DR PRIDE; D7PI16; -.
DR BioCyc; MetaCyc:MON-19268; -.
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 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..419
FT /note="O-methyltransferase gsfB"
FT /id="PRO_0000436721"
FT ACT_SITE 320
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 255..256
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
FT BINDING 278
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 300..301
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
FT BINDING 316
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
SQ SEQUENCE 419 AA; 46712 MW; 93E65FC137183111 CRC64;
MASNTSRSAH LAQIITENTA NIETYRREQG LPPLSLGPDA PLDVKYPPNV EKCRRAVIDA
TLELGELATG PVELRLVPGW AIMTMFGVTQ FICDFDIARQ IPLAGDISYE DLSKAINVAV
PVLRQVLRAG MPYHMFYESR PGHVAHTATT KVMASESLIS DWTSLYTDVL FPASAGLSKA
LREEPTASDP SKTGFMVTKG DGESGMYMYF EKHPEEARRF AGVMEAFQKD EAYAVRHLTD
SWPSDSQTGK LVDLGGSTGA VAFALAEKFP GLEIVVQDLP GALEAAHVRE GKNVSFMPHD
FFNEQPVKDA DVYMFRWILH NWPDGHVQRI LRALVPSLKP GAKVIVFDEI MPPAGTLPLS
IERYQRNIDF GMLTLFNSKI RDIVEWKEII TQSDQRFNVT GVRYPENSRL SLIEIVWQP
