GSFE_PENAE
ID GSFE_PENAE Reviewed; 377 AA.
AC D7PI19;
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=Short chain dehydrogenase gsfE {ECO:0000303|PubMed:20534346};
DE EC=1.-.-.- {ECO:0000269|PubMed:23978092};
DE AltName: Full=Griseofulvin synthesis protein E {ECO:0000303|PubMed:20534346};
GN Name=gsfE {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: Short chain dehydrogenase; 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 -!- 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 dehydrogriseofulvin and dechloro-
CC dehydrogriseofulvi (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 short-chain dehydrogenases/reductases (SDR)
CC family. Highly divergent. {ECO:0000305}.
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DR EMBL; GU574478; ADI24957.1; -; Genomic_DNA.
DR AlphaFoldDB; D7PI19; -.
DR SMR; D7PI19; -.
DR BioCyc; MetaCyc:MON-19273; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW NADP; Nucleotide-binding; Oxidoreductase.
FT CHAIN 1..377
FT /note="Short chain dehydrogenase gsfE"
FT /id="PRO_0000436724"
FT ACT_SITE 125
FT /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT ACT_SITE 153
FT /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT BINDING 11..13
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT BINDING 39..40
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT BINDING 57..58
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT BINDING 121
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT BINDING 179
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT BINDING 187..189
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
SQ SEQUENCE 377 AA; 42538 MW; 74030079D4B61250 CRC64;
MPKTAFITGA NGLSGSAIVE YLCNTTTSDD WGSIIVTSRS PFKSTVMDPR IKFIALDFVN
DVSSLVETMK EVCGAVTHAY FCSYLHKDDF AESYTVNKAL FENFIAAIDK AAPKLENVTL
QTGGKYYNLH VEPVPSPARE NDPRRYGPFE NFYFTQEDTL AEMQRGKTWS WNVIRPEAII
GANSQPYGLN VALTIAMYFL ICRELGSASP MPTNQRYWEG TDDVSYAPLI ADLTIFVSTR
KSCANEAFNV TNGDYFTWRY MWPRLAASLG AKADSQQCFE KPMPGEGELQ LDWSLAEWCK
DKRKVWEDLC DRQGLPGAKA TFDLAGWAVG DFLYQRTWSA TLSVNKARRF GWTGHMDSYQ
SFVDTFDKFR QLGLIPK
