ID   NTNM_NECSZ              Reviewed;         516 AA.
AC   A0A455LLV8;
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 ntnM {ECO:0000303|PubMed:29797385};
DE            EC=1.-.-.- {ECO:0000305|PubMed:29797385};
DE   AltName: Full=Nectripenoid biosynthesis cluster protein M {ECO:0000303|PubMed:29797385};
GN   Name=ntnM {ECO:0000303|PubMed:29797385};
OS   Nectria sp.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Hypocreomycetidae; Hypocreales; Nectriaceae; Nectria.
OX   NCBI_TaxID=1755444;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND PATHWAY.
RC   STRAIN=Z14-w;
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 nectripenoids A and B,
CC       as well as cochliquninone D and isocochliquninone E (PubMed:29797385).
CC       The pathway probably begins with the HR-PKS ntnH that catalyzes two
CC       chain-extension steps to form a reduced triketide, which then primes
CC       the SAT domain in the NR-PKS ntnG to initiate three more cycles of
CC       extension to give a linear hexaketide corresponding to the polyketide
CC       part of nectripenoids (Probable). The FAD-dependent monooxygenase ntnJ
CC       then performs an oxidative decarboxylation at C11 of the ntnH/ntnG
CC       product, via an electrophilic aromatic hydroxylation with concomitant
CC       ipso-decarboxylation (Probable). The membrane-bound polyprenyl
CC       transferase ntnF then introduces a farnesyl group before the FAD-
CC       dependent monooxygenase ntnK functions as the first epoxidase on
CC       terminal C12'-C13' olefin, followed by a second epoxidation on C7'-C8'
CC       catalyzed by ntnA (Probable). The terpene cyclase/mutase ntnI then
CC       initiates the sequential tricyclic ring formation through protonation
CC       of the terminal epoxide and catalyzes the regioselective and
CC       stereoselective 6/6/6-tricyclic ring formation (Probable). The
CC       cytochrome P450 monooxygenase ntnM may then hydroxylate C1' (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:0000305|PubMed:29797385}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; MH183006; AYO60873.1; -; mRNA.
DR   AlphaFoldDB; A0A455LLV8; -.
DR   SMR; A0A455LLV8; -.
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; -; 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   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..516
FT                   /note="Cytochrome P450 monooxygenase ntnM"
FT                   /id="PRO_0000452573"
FT   TRANSMEM        22..42
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         453
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   516 AA;  58770 MW;  0B444CB928E0C632 CRC64;
     MFGDFVEKLP QKLPQKLDIP LIINVILSIA AIALIRALAI SILRQYRLRK LPLVNGVGVF
     ESSQKAKQNF LFNAEGLLEN GFTKSTKAFR MATDDSEVLI LSPDYIDEIR NDKRLSLTHA
     LAEDFLGHIP AFVNFSPQKG LNDMAGDILQ KKLTQSLDLS TEAALALQEQ WTDNKEWHAL
     NAKTTMVEIV ARISSRVFLG LELCRNPAWL RITADYTVNV FFGVMALKKW PKYLHPFVWR
     FVPEVRTVRD QIQEAVNLIQ PVVEKRTAEG KSPSSRKTYS DTIQWANELA NGRPYDPALL
     QLGFSLAAIH TTSDLLSQIL YNICAYPEYI DPLREEIVTV LKEHGMTKAG LFKMKLMDSI
     MKESQRLKPG AMLMMRRMVL EDITLSNGVF LPRGVQIGIP TRSHFDPSFY TDPERFDGYR
     YVKMDDDPQR EKSRHFVSTS PEHLAFGHGK HACPGRFFAS QEIKIALCHI LMKYEFKLAD
     GSKPTVMKMG WVLSSDPMVQ LMVRKREGVD ENLLYK