IACC_PESFW
ID IACC_PESFW Reviewed; 272 AA.
AC A0A1J0HSK7; W3XJ18;
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 iacC {ECO:0000303|PubMed:29384350};
DE EC=1.1.1.- {ECO:0000305|PubMed:29384350};
DE AltName: Full=Iso-A82775C biosynthesis cluster protein C {ECO:0000303|PubMed:29384350};
GN Name=iacC {ECO:0000303|PubMed:29384350}; ORFNames=PFICI_04039;
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, PATHWAY, AND BIOTECHNOLOGY.
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: Abolishes the production of iso-A82775C, but
CC accumulates pestalofone A. {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; APC57595.1; -; Genomic_DNA.
DR EMBL; KI912110; ETS86014.1; -; Genomic_DNA.
DR RefSeq; XP_007830811.1; XM_007832620.1.
DR AlphaFoldDB; A0A1J0HSK7; -.
DR SMR; A0A1J0HSK7; -.
DR EnsemblFungi; ETS86014; ETS86014; PFICI_04039.
DR GeneID; 19269052; -.
DR KEGG; pfy:PFICI_04039; -.
DR eggNOG; KOG1611; Eukaryota.
DR HOGENOM; CLU_010194_9_2_1; -.
DR OMA; IRSTWEK; -.
DR OrthoDB; 1390068at2759; -.
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; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW NAD; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..272
FT /note="Short-chain dehydrogenase/reductase iacC"
FT /id="PRO_0000451378"
FT ACT_SITE 169
FT /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT BINDING 10..12
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT BINDING 32..33
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT BINDING 34..35
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT BINDING 127
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT BINDING 134..136
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
SQ SEQUENCE 272 AA; 29215 MW; 1688C86AFD41A6B8 CRC64;
MSVYVITGAS KGIGFGFVKS ISEDPANLVV GLVRDKAATE KKVAEELGGR TNIHILHGDL
TSYESLKQAA ADTAKIVGER GVDYLVANGA YPSQFDAYVP IGALGDQVEE LEEVSAKLFK
TNVVGNIHLF NLFIPLVKQS KAKKVIAISS GHGDLDWINN NDIEISSLYG ASKAALNVVV
AKFSVQYKPE GVLFFSLSPG AVEVGHYDNV SPEQVQGLMG FMGKIQAYAP HFKGAVPVED
AVRTIRATWE RASIETGYAG AFVSQHGNKQ WL
