ATNM_ARTSZ
ID ATNM_ARTSZ Reviewed; 480 AA.
AC A0A455LM27;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-JUN-2019, sequence version 1.
DT 03-AUG-2022, entry version 14.
DE RecName: Full=Cytochrome P450 monooxygenase atnM {ECO:0000303|PubMed:29797385};
DE EC=1.-.-.- {ECO:0000305|PubMed:29797385};
DE AltName: Full=Arthripenoid biosynthesis cluster protein M {ECO:0000303|PubMed:29797385};
GN Name=atnM {ECO:0000303|PubMed:29797385};
OS Arthrinium sp.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Xylariomycetidae; Xylariales; Apiosporaceae; Arthrinium;
OC unclassified Arthrinium.
OX NCBI_TaxID=1756131;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], DISRUPTION PHENOTYPE, FUNCTION, AND PATHWAY.
RC STRAIN=NF2194;
RX PubMed=29797385; DOI=10.1002/anie.201804317;
RA Zhang X., Wang T.T., Xu Q.L., Xiong Y., Zhang L., Han H., Xu K., Guo W.J.,
RA Xu Q., Tan R.X., Ge H.M.;
RT "Genome mining and comparative biosynthesis of meroterpenoids from two
RT phylogenetically distinct fungi.";
RL Angew. Chem. Int. Ed. 57:8184-8188(2018).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of the meroterpenoids arthripenoids
CC (PubMed:29797385). The pathway begins with the HR-PKS atnH that
CC catalyzes two chain-extension steps to form a reduced triketide, which
CC then primes the SAT domain in the NR-PKS atnG to initiate three more
CC cycles of extension to give a linear hexaketide corresponding to the
CC polyketide part of arthripenoids (PubMed:29797385). The FAD-dependent
CC monooxygenase atnJ then performs an oxidative decarboxylation at C11 of
CC the atnH/atnG product, via an electrophilic aromatic hydroxylation with
CC concomitant ipso-decarboxylation (PubMed:29797385). The membrane-bound
CC polyprenyl transferase atnF then introduces a farnesyl group before the
CC FAD-dependent monooxygenase atnK functions as the first epoxidase on
CC terminal C12'-C13' olefin, followed by a second epoxidation on C7'-C8'
CC catalyzed by atnA (PubMed:29797385). The terpene cyclase/mutase atnI
CC then initiates the sequential tricyclic ring formation through
CC protonation of the terminal epoxide and catalyzes the regioselective
CC and stereoselective 6/6/6-tricyclic ring formation (PubMed:29797385).
CC The cytochrome P450 monooxygenase atnM is responsible for hydroxylating
CC both C1' and C10' (Probable). The next steps may involve ketoreduction
CC and acetyl transfer by the ketoreductase atnB and the acetyltransferase
CC atnC, and lead to the production of arthripenoid B, the final
CC biosynthetic product of the atn cluster (PubMed:29797385). The
CC hydroquinone moiety in arthripenoid B is prone to undergo spontaneous
CC oxidation to afford a benzoquinone compound, a key intermediate for
CC generating structure diversity (Probable). For instance, addition of a
CC cysteine followed by ring contraction gives arthripenoid A,
CC tautomerization gives the main product arthripenoid C, addition of a
CC molecular of water or amine affords arthripenoid D or E, respectively,
CC and loss of one water forms arthripenoid F (Probable).
CC {ECO:0000269|PubMed:29797385, ECO:0000305|PubMed:29797385}.
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:29797385}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of arthripenoids but
CC leads to the accumulation of a new compounds that have no hydroxy
CC groups at C1' and C10' positions. {ECO:0000269|PubMed:29797385}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; MH183019; AYO60886.1; -; mRNA.
DR AlphaFoldDB; A0A455LM27; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.630.10; -; 2.
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 Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 2: Evidence at transcript level;
KW Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..480
FT /note="Cytochrome P450 monooxygenase atnM"
FT /id="PRO_0000452572"
FT TRANSMEM 17..34
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 418
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"
SQ SEQUENCE 480 AA; 54264 MW; E728F74D96430A39 CRC64;
MLDIPLSESL QHPGTRVAVN IIISIAAIAL VRVIGSRWLT QYHLRALPLV NGLGLFESGK
RAKGSFLFNA QGLLDEGYAK SSKAFRVQTD SEQVVVLAPE CASEIRNDDR FSFTNLLAED
FLAHIPAFVN FSPHNGLNDM ANDVITKKLN PALGLVTPDL SAEATLTFRD HWTDSTEWHS
VNVKGTILEI VARLSSRVFL GPELCRNPAW LRITVDYTTN LFFGVVALKK WRSFLHPLVW
RFVPEVRKVR QQIEEAIQLI QPVVDKRHAE SRSSAASSGK KDQTLYDLCS YPEYIEPLRD
ELVTVLKESG MTKAGLFKLK LMDSFMKESQ RFKPGAMIMM RRKVMEDVTL SNGVFLPRGV
QVGIPLRSHF NPKAYSDPDK FDGYRYVKMA DDPEKEVFRH FVTTSQEHMG FGFGKHSCPG
RFFAANEVKV ALCHILLKYD FKLAEGPKPN VMKMGWVLIS DPMTNLMIKR REGIDESILE
