ID   IACF_PESFW              Reviewed;         204 AA.
AC   A0A1J0HSL4; W3XIX3;
DT   02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT   15-FEB-2017, sequence version 1.
DT   25-MAY-2022, entry version 7.
DE   RecName: Full=Oxidoreductase iacF {ECO:0000303|PubMed:29384350};
DE            EC=1.-.-.- {ECO:0000305|PubMed:29384350};
DE   AltName: Full=Iso-A82775C biosynthesis cluster protein F {ECO:0000303|PubMed:29384350};
GN   Name=iacF {ECO:0000303|PubMed:29384350}; ORFNames=PFICI_04043;
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: Oxidoreductase; part of the gene cluster that mediates the
CC       biosynthesis of iso-A82775C, a enylepoxycyclohexane and biosynthetic
CC       precursor of the chloropestolide anticancer natural products
CC       (PubMed:29384350). Within the cluster, the prenyltransferase iacE
CC       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 pestalodiol E. {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 oxidoreductase OpS7 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=ETS86018.1; Type=Erroneous termination; Note=Extended C-terminus.; Evidence={ECO:0000305};
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DR   EMBL; KU963195; APC57598.1; -; Genomic_DNA.
DR   EMBL; KI912110; ETS86018.1; ALT_SEQ; Genomic_DNA.
DR   RefSeq; XP_007830815.1; XM_007832624.1.
DR   AlphaFoldDB; A0A1J0HSL4; -.
DR   EnsemblFungi; ETS86018; ETS86018; PFICI_04043.
DR   GeneID; 19269056; -.
DR   KEGG; pfy:PFICI_04043; -.
DR   eggNOG; ENOG502SJU9; Eukaryota.
DR   HOGENOM; CLU_089363_0_0_1; -.
DR   OrthoDB; 1423082at2759; -.
DR   Proteomes; UP000030651; Unassembled WGS sequence.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   Gene3D; 2.60.120.10; -; 1.
DR   InterPro; IPR014710; RmlC-like_jellyroll.
DR   InterPro; IPR011051; RmlC_Cupin_sf.
DR   SUPFAM; SSF51182; SSF51182; 1.
PE   1: Evidence at protein level;
KW   Oxidoreductase; Reference proteome.
FT   CHAIN           1..204
FT                   /note="Oxidoreductase iacF"
FT                   /id="PRO_0000451385"
SQ   SEQUENCE   204 AA;  23563 MW;  1C32047B0DAA2D78 CRC64;
     MVWAWQQWLS PRPQKRTKNT SQVAFYTSEN AALYEPLSKP DGNWYVRETH FRENPNVRAG
     LTGPPLHLHL QQDEYFKVEQ GVLGAVKDGV EVAITKNDPV LHIPRGTRHR FWPHPSSTED
     LVFTAWADPC KDHDHILDLN FLRNLAGYLA DCDSEGLQPS PFQLILFFHE ASSILCPPFL
     NWMPLWLLIW VHNGLAWIAR EFLG