IACH_PESFW
ID IACH_PESFW Reviewed; 512 AA.
AC A0A1J0KJK5; W3XJ25;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2017, sequence version 1.
DT 25-MAY-2022, entry version 13.
DE RecName: Full=FAD-linked oxidoreductase iacH {ECO:0000303|PubMed:29384350};
DE EC=1.-.-.- {ECO:0000305|PubMed:29384350};
DE AltName: Full=Iso-A82775C biosynthesis cluster protein HK {ECO:0000303|PubMed:29384350};
DE Flags: Precursor;
GN Name=iacH {ECO:0000303|PubMed:29384350}; ORFNames=PFICI_04045;
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: FAD-linked oxidoreductase; part of the gene cluster that
CC mediates the biosynthesis of iso-A82775C, a enylepoxycyclohexane and
CC 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 -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q5BEJ5};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|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: Does not affect the production of iso-A82775C.
CC {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 oxygen-dependent FAD-linked oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; KU963195; APC93982.1; -; Genomic_DNA.
DR EMBL; KI912110; ETS86020.1; -; Genomic_DNA.
DR RefSeq; XP_007830817.1; XM_007832626.1.
DR AlphaFoldDB; A0A1J0KJK5; -.
DR SMR; A0A1J0KJK5; -.
DR STRING; 1229662.W3XJ25; -.
DR EnsemblFungi; ETS86020; ETS86020; PFICI_04045.
DR GeneID; 19269058; -.
DR KEGG; pfy:PFICI_04045; -.
DR eggNOG; ENOG502SJ3M; Eukaryota.
DR HOGENOM; CLU_018354_0_1_1; -.
DR OMA; KFRWYNP; -.
DR OrthoDB; 350817at2759; -.
DR Proteomes; UP000030651; Unassembled WGS sequence.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Glycoprotein; Oxidoreductase; Reference proteome;
KW Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..512
FT /note="FAD-linked oxidoreductase iacH"
FT /id="PRO_5009613882"
FT DOMAIN 77..248
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 69
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 210
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 217
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 278
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 295
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 367
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 512 AA; 56516 MW; 4D4B0FBCDD32BE1F CRC64;
MVSLKACVVA YGFTLLPALV SGSPLVPRYF QKHLVSRCNI SAITVQSELG PQLSNTSLIF
GPDNVLFPNA TERWNTLDTP DVQLVVQPAA ESDISKIVKY CNDNSIEFLV RNRGHGTTTS
LSAFSGIEIN VELLQGITIQ PDGETAIFQA GTYGAEVINT LWDQGYVTTT GSTACVGLTG
PSLGGGHSRY EGLYGLVMDN IVHYNIVLAN GTEIGVNETS HPDLMWALKG AGHNFAIVTS
LEKKIYPGEN WHQHTYTWTQ DKLETVFEAL NTFHKSYNGT TPPKMGVNYG AIIMNTSYST
TEAVMEWGFQ YAGPGDEAEA LLAPFNAIGA IAEDQFDASY PTIAGTTSET CGSAKRAISS
AMTLDYNITT ERALYDHFVA KVAEYPDLAA TAYLWHEGYS TEGYQIIPED STAYPHREEN
HLMVFFTEVP EDSDLLEPAL DWAKEAMDLW NGGQPDRLPS TYVNYAQGAD YETLESVYGY
ESWRLERLRS LKAEYDPENR FRYFVPIISD EA
