ID   GSFK_PENAE              Reviewed;         251 AA.
AC   D7PI11;
DT   06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT   10-AUG-2010, sequence version 1.
DT   03-AUG-2022, entry version 29.
DE   RecName: Full=Short chain dehydrogenase gsfK {ECO:0000303|PubMed:20534346};
DE            EC=1.-.-.- {ECO:0000305|PubMed:20534346};
DE   AltName: Full=Griseofulvin synthesis protein K {ECO:0000303|PubMed:20534346};
GN   Name=gsfK {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.
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). The exact role of
CC       gsfK within the pathway has not been identified yet (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   -!- 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. {ECO:0000305}.
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DR   EMBL; GU574478; ADI24951.1; -; Genomic_DNA.
DR   AlphaFoldDB; D7PI11; -.
DR   SMR; D7PI11; -.
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   InterPro; IPR002347; SDR_fam.
DR   Pfam; PF00106; adh_short; 1.
DR   PRINTS; PR00081; GDHRDH.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   1: Evidence at protein level;
KW   NADP; Nucleotide-binding; Oxidoreductase.
FT   CHAIN           1..251
FT                   /note="Short chain dehydrogenase gsfK"
FT                   /id="PRO_0000436725"
FT   ACT_SITE        161
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         35..36
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT   BINDING         142
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
SQ   SEQUENCE   251 AA;  26235 MW;  25C1636B607A25F6 CRC64;
     MPATVLITGG NRGLGKGLVA TYLSTPDTTV IATVRDPSKC ESLSALPKAL GSNLLLVKLE
     VTSKDSITTA IGTLDTHNIG SIDVVIANAG ISGPTSSLAE APVSELQRYI DVNAYGPFEL
     FKAVLPLLRS SNSGNKAKFV CISSAGGSLA AMYNFMPISA YGASKALANF LVKWLALDNK
     DIIIWAQNPG SVDTDMARDG LDLAKSLGFD LSSLSFTSPE ESACAIKKLI DGATTEMSGK
     FLDHDGSELA W