NTNK_NECSZ
ID NTNK_NECSZ Reviewed; 760 AA.
AC A0A455M7R7;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-JUN-2019, sequence version 1.
DT 03-AUG-2022, entry version 11.
DE RecName: Full=FAD-dependent monooxygenase ntnK {ECO:0000303|PubMed:29797385};
DE EC=1.-.-.- {ECO:0000305|PubMed:29797385};
DE AltName: Full=Nectripenoid biosynthesis cluster protein K {ECO:0000303|PubMed:29797385};
GN Name=ntnK {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: FAD-dependent 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=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:A6T923};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000305|PubMed:29797385}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; MH183003; AYO60870.1; -; mRNA.
DR AlphaFoldDB; A0A455M7R7; -.
DR SMR; A0A455M7R7; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 2: Evidence at transcript level;
KW FAD; Flavoprotein; Glycoprotein; Membrane; Monooxygenase; Oxidoreductase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..760
FT /note="FAD-dependent monooxygenase ntnK"
FT /id="PRO_0000452554"
FT TRANSMEM 18..38
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 460..480
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 492..512
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 527..547
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 570..590
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 599..619
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 641..661
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 725..745
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 47..48
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 141
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 318
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 328..332
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT CARBOHYD 518
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 621
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 760 AA; 85745 MW; B107E15C1271E3B0 CRC64;
MTLKAVVGND KGARFRVVIV GGSIAGLVLA HCLHHAGIDY LVLEARDRVD PQVGASIGIF
SNGARILDQL GVYKSIEQLT ESPVWYNMLT GEGALVQKVD SLRLIEARTG YPVTFLDRQQ
VLKILYDQLP TKSKVLTSKR VLSVDHLAND IRVRCEDGTE FTGDIVAGAD GVHSRIRREM
WRHAERNNAL RYLKKDQEAM SAEYRCLFGI STAVPGLAGK SHYRTFNKDW SFLIAIGKDN
RCYWFVFEKL DATRRPPTMP RYSESDQKEF VRPFLKRYVS QTVTFDAVWE NKISSALTVL
EEAQYNHWTY DRIVCLGDAI HKMTPNIGQG GNWAIESAAA LTNKLHVMTK TTNQPTIEHI
RATLREYEQS RQPRTKEVCE TAGFATRLEA FSSFWHRVMS LYVVPYAGDM LVDVHCQAVA
QAPKLDFLPL PDKSLRDGTI FRIAQLGGQE DKPIWRVLRA LPFILLCIAA YNTMGSTTLV
PHVHQMSSTE RICLVEFLGD LTPLYIIAMV ESVRRGNNFT IAVLWSLFGL VGQSKGIVYA
VPLYFFLHYV QCSMVRCSSP DNRHVPIHYA STLVAAVGAG YLLPTAIVLF GSTNLDVSYL
WKLFPILMTI LHRVFASFAP NTSAVDRIEN PRADMRYLRL AYGIGGILAG ITRVYFWITP
VHHMANLLSD MLQLWHEPLA LRNVDLRQLI RHNHLLVLGS GLFWELLHFR DLKNARRLKA
SWIKVLGVLA TTVVIFGPGS AMALGWAWRE EVLASKIQLN
