ID   IACG_PESFW              Reviewed;         248 AA.
AC   A0A1J0HSP5; W3XJ23;
DT   02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT   15-FEB-2017, sequence version 1.
DT   03-AUG-2022, entry version 11.
DE   RecName: Full=Short-chain dehydrogenase/reductase iacG {ECO:0000303|PubMed:29384350};
DE            EC=1.1.1.- {ECO:0000305|PubMed:29384350};
DE   AltName: Full=Iso-A82775C biosynthesis cluster protein G {ECO:0000303|PubMed:29384350};
GN   Name=iacG {ECO:0000303|PubMed:29384350}; ORFNames=PFICI_04044;
OS   Pestalotiopsis fici (strain W106-1 / CGMCC3.15140).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Xylariomycetidae; Xylariales; Sporocadaceae; Pestalotiopsis.
OX   NCBI_TaxID=1229662;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE,
RP   INDUCTION, AND PATHWAY.
RC   STRAIN=W106-1 / CGMCC3.15140;
RX   PubMed=29384350; DOI=10.1021/acschembio.7b01059;
RA   Pan Y., Liu L., Guan F., Li E., Jin J., Li J., Che Y., Liu G.;
RT   "Characterization of a prenyltransferase for iso-A82775C biosynthesis and
RT   generation of new congeners of chloropestolides.";
RL   ACS Chem. Biol. 13:703-711(2018).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=W106-1 / CGMCC3.15140;
RX   PubMed=25623211; DOI=10.1186/s12864-014-1190-9;
RA   Wang X., Zhang X., Liu L., Xiang M., Wang W., Sun X., Che Y., Guo L.,
RA   Liu G., Guo L., Wang C., Yin W.B., Stadler M., Zhang X., Liu X.;
RT   "Genomic and transcriptomic analysis of the endophytic fungus
RT   Pestalotiopsis fici reveals its lifestyle and high potential for synthesis
RT   of natural products.";
RL   BMC Genomics 16:28-28(2015).
CC   -!- FUNCTION: Short-chain dehydrogenase/reductase; part of the gene cluster
CC       that mediates the biosynthesis of iso-A82775C, a enylepoxycyclohexane
CC       and biosynthetic precursor of the chloropestolide anticancer natural
CC       products (PubMed:29384350). Within the cluster, the prenyltransferase
CC       iacE prenylates siccayne to generate pestalodiol E, using dimethylallyl
CC       diphosphate (DMAPP) as cosubstrate (PubMed:29384350). The probable
CC       oxidoreductase iacF is then involved in the epoxidation of pestalodiol
CC       F to pestalodiol F, which is further converted to pestalofone A by the
CC       short-chain dehydrogenase/reductase iacG (PubMed:29384350). Iso-A82775C
CC       is subsequently generated from pestalofone A by the short-chain
CC       dehydrogenase/reductase iacC (PubMed:29384350). Iso-A82775C is further
CC       condensed with maldoxin via a Diels-Alder reaction to produce the
CC       anticancer natural products chloropestolides A to E (Probable).
CC       {ECO:0000269|PubMed:29384350, ECO:0000305|PubMed:29384350}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:29384350}.
CC   -!- INDUCTION: Expression is co-regulated with the other genes from the
CC       iso-A82775C biosynthesis cluster and probably controlled by the
CC       cluster-specific transcription factors iacI and iacK.
CC       {ECO:0000269|PubMed:29384350}.
CC   -!- DISRUPTION PHENOTYPE: Reduced strongly the production of iso-A82775C
CC       and accumulates pestalodiol F. {ECO:0000269|PubMed:29384350}.
CC   -!- BIOTECHNOLOGY: Iso-A82775C is a precursor for the biosynthesis of the
CC       anticancer natural products chloropestolides A to E via a Diesls-Alder
CC       reaction with maldoxin (PubMed:29384350). In the absence of the
CC       prenyltransferase iacE, siccayne accumulates instead of iso-A82775C and
CC       can also be condensed with maldoxin to produce chloropestolides H to K,
CC       which show also antibacterial and anticancer properties
CC       (PubMed:29384350). {ECO:0000269|PubMed:29384350}.
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
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DR   EMBL; KU963195; APC57599.1; -; Genomic_DNA.
DR   EMBL; KI912110; ETS86019.1; -; Genomic_DNA.
DR   RefSeq; XP_007830816.1; XM_007832625.1.
DR   AlphaFoldDB; A0A1J0HSP5; -.
DR   SMR; A0A1J0HSP5; -.
DR   EnsemblFungi; ETS86019; ETS86019; PFICI_04044.
DR   GeneID; 19269057; -.
DR   KEGG; pfy:PFICI_04044; -.
DR   eggNOG; ENOG502SMMV; Eukaryota.
DR   HOGENOM; CLU_078552_0_0_1; -.
DR   OMA; TVEANIC; -.
DR   OrthoDB; 1269323at2759; -.
DR   Proteomes; UP000030651; Unassembled WGS sequence.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR002347; SDR_fam.
DR   Pfam; PF00106; adh_short; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   1: Evidence at protein level;
KW   NAD; NADP; Oxidoreductase; Reference proteome.
FT   CHAIN           1..248
FT                   /note="Short-chain dehydrogenase/reductase iacG"
FT                   /id="PRO_0000451379"
FT   ACT_SITE        159
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         33..34
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
SQ   SEQUENCE   248 AA;  26817 MW;  D45586AA33164259 CRC64;
     MTETVLVIGA TGHIGVSAVI GALRTKRNVL AVVRNAAAVD KLFRLAGTRD GITTVEADIT
     SEHGLQSVVD KVKNGELPAF QHVYSAVGGV KTTTPLKDLS IEDFRANMSI NFDTNFFAYR
     ATIGYLLSQS NPTTYTVITG AIGDVGIWPG PAMSQGALYS LGISAELENR DTNVRFNEMY
     LAFPVMVDEE AVKEEAAKMG VVKASDFARS YENLLAKDEI KGSRIFIFTP GDIDTLRWES
     KAFKGPPS