ANDK_EMEVA
ID ANDK_EMEVA Reviewed; 865 AA.
AC A0A097ZPE4;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 07-JAN-2015, sequence version 1.
DT 03-AUG-2022, entry version 22.
DE RecName: Full=Cytochrome P450 monooxygenase andK {ECO:0000303|PubMed:25216349};
DE EC=1.-.-.- {ECO:0000269|PubMed:25216349};
DE AltName: Full=Anditomin synthesis protein K {ECO:0000303|PubMed:25216349};
DE Flags: Precursor;
GN Name=andK {ECO:0000303|PubMed:25216349};
OS Emericella variicolor (Aspergillus stellatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX NCBI_TaxID=1549217;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 12069 / CBS 136.55 / IMI 60316 / NBRC 32302;
RX PubMed=25216349; DOI=10.1021/ja508127q;
RA Matsuda Y., Wakimoto T., Mori T., Awakawa T., Abe I.;
RT "Complete biosynthetic pathway of anditomin: nature's sophisticated
RT synthetic route to a complex fungal meroterpenoid.";
RL J. Am. Chem. Soc. 136:15326-15336(2014).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of anditomin, a fungal meroterpenoid
CC (PubMed:25216349). The first step of the pathway is the synthesis of
CC 3,5-dimethylorsellinic acid (DMOA) by the polyketide synthase andM
CC (PubMed:25216349). DMOA is then converted to the phthalide compound
CC 5,7-dihydroxy-4,6-dimethylphthalide (DHDMP) by the cytochrome P450
CC monooxygenase andK, which is further prenylated by the
CC prenyltransferase andD to yield farnesyl-DHDMP (PubMed:25216349).
CC Further epoxidation by the FAD-dependent monooxygenase andE leads to
CC epoxyfarnesyl-DHDMP (PubMed:25216349). The next step involves the
CC terpene cyclase andB that converts epoxyfarnesyl-DHDMP into preandiloid
CC A through opening of the epoxide ring followed by the cyclization of
CC the farnesyl moiety (PubMed:25216349). Preandiloid A is in turn
CC oxidized at the C-3 hydroxyl group to yield preandiloid B by the
CC dehydrogenase andC (PubMed:25216349). The dioxygenase andA is solely
CC responsible for the dehydrogenation of preandiloid B leading to the
CC enone preandiloid C, as well as for the intriguing structural
CC rearrangement to generate the bicyclo[2.2.2]octane core, transforming
CC preandiloid C into andiconin (PubMed:25216349). FAD-binding
CC monooxygenase andJ then produces andilesin D which is reduced by
CC dehydrogenase andI to yield andilesin A (PubMed:25216349). Action of
CC acetyltransferase andG followed by a spontaneous acetate elimination
CC leads then to andilesin B, which is in turn substrate of the short
CC chain dehydrogenase andH to yield andilesin C (PubMed:25216349).
CC Finally, the dioxygenase andF catalyzes the transformation of andilesin
CC C to anditomin (PubMed:25216349). {ECO:0000269|PubMed:25216349}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:25216349}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB981314; BAP81865.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A097ZPE4; -.
DR SMR; A0A097ZPE4; -.
DR BioCyc; MetaCyc:MON-19042; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.630.10; -; 1.
DR Gene3D; 3.60.15.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR InterPro; IPR001279; Metallo-B-lactamas.
DR InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR Pfam; PF00753; Lactamase_B; 1.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR PRINTS; PR00385; P450.
DR SMART; SM00849; Lactamase_B; 1.
DR SUPFAM; SSF48264; SSF48264; 1.
DR SUPFAM; SSF56281; SSF56281; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..865
FT /note="Cytochrome P450 monooxygenase andK"
FT /id="PRO_0000436587"
FT BINDING 448
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 510
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 604
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 667
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 865 AA; 96673 MW; C6232B4AC2D0EC04 CRC64;
MMPTVTAVSA ILPLAILFVF SRALWKLWYL SDIPGPFWCK LTNIPRLCWV RTGRAHDIHY
ELHKEYGKLV RIGPSMISIS DPAALSTVYP TRMGVPKSDF YKTQRPYVPG TGALPVVFNT
QNEELHKELR GPVSSLYAMS NVMKLEPLMD ETLQVLFDQI DARFVSGTKA FDLSNWLQFF
AFEVMGTISF SKKYGFLEAG RDFNGLLSGI WGFMKSAAPM GQMPWLDDVL YKNALAAKLR
GTTGMPVLRI VNKYITERIT GHAKASSDHA DMLSQFLDIQ ASNEKVPTWA PKAWTFSNVI
AGSDSSANSM TTVMYNLMTH PETMARLYQE LSEAKQQAGN VTAHILPWTS IRDLPYLDAC
VMEAFRIHPA FCLHLERLVP ETGMEICGKQ IPPGAIVGMS PWVINRHKPT FGEDVHQWRP
ERWLGHSETR LQELKNTILT FGYGRRVCLG KNIAIMEIKK LISSLVLNYE WTVIDPSEYR
VENKWFFKQS GFDVTVKHRS SVRHTPRATN MTKVPPTLAI PASSSTVEVR VINTRTIMRT
DHSLLWKSPV EGFKGLDLPI YAFLISNGNR HIIFDLGLRQ DYENLPPRIA GLLKNAPYIV
TEANVSEILD SDDTGLDIKG RDIEAVIWSH HHYDHTGDPS TFPPSTKLVV GPGVLSLTGG
GYPKNPNTTV LETDLSGRKI QEISFDAQAD SSVKVGPFDG VDYFGDGSFY LLNAPGHSVG
HMCGLARVTT APDTFIFMAA DGCHHPGAIR PSEYMALPRD IPKSLVRKLR TAEADSGGKA
QDGDTKPLLP FLPALFPDYT QAMETVEKIK QLDACDNVFV ILPHDGSLLG AIDFFPRPIN
DWKKKGLKES TRWKFCQEME EALSG
