NTNA_NECSZ
ID NTNA_NECSZ Reviewed; 754 AA.
AC A0A455LLV4;
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 ntnA {ECO:0000303|PubMed:29797385};
DE EC=1.-.-.- {ECO:0000305|PubMed:29797385};
DE AltName: Full=Nectripenoid biosynthesis cluster protein A {ECO:0000303|PubMed:29797385};
GN Name=ntnA {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; MH182997; AYO60864.1; -; mRNA.
DR AlphaFoldDB; A0A455LLV4; -.
DR SMR; A0A455LLV4; -.
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..754
FT /note="FAD-dependent monooxygenase ntnA"
FT /id="PRO_0000452556"
FT TRANSMEM 3..23
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 446..466
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 486..506
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 536..556
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 563..583
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 595..615
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 644..664
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 679..697
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 712..732
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 35..36
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 311
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 321..325
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT CARBOHYD 586
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 616
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 701
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 754 AA; 83513 MW; 9ACFCE11B5035C20 CRC64;
MAIPFKVLII GGGVAGLTLA IMLEAYGFDY ELLEKHSDVA PKLGAGVGLT PNGARILDQI
GVWEMMCERS SPVDSGTALS PEGRTVIFNP NMGEWLQKLF GYKIHFLSRH DCLKILFNKI
QQKSRVHLLK EVIKIEAGNL GEKGYVETKD GSIYTGDIII GADGVRSSVR RELWRIADSE
SPGYIPKQDK TGIVSFYTAV VGIAYNSGLP EGGSARAYNH HRSYFFQEGR EGSGEFYWWL
CAKNEKTKEG VIPKLSSEVK EGLLNKYKND QIGPDLTLGA LYKSSIYSTV IPLQEFVLQK
CFYKNILLIG DTFRKLHPVA GQGANSAIEE SAFVADMLWD LRERGALHDP DSIQKALTEF
QTERVVRTTA LREDANLVQR MESLDNPVMK FMALKFIPRL NFVIAFLPQL GSSFTPARHL
KHLRPPKVGL CPFSQDMKAK PLPRSPLATF SWVTVLILAA SSPWLASKYF ISGARSFTDD
QASQLAEVLE LYISILSVSI SGMWVIESYK TSSLISPFTS SLPWILASNF WGWQKILPIY
ICFYILSSQS VVYYYMPQTM TDLGVAKALL PALLVVYTVS AVCTINESGG NTDNSWWFTA
DFAFPVVAYL SGMFLNATST MPQAVDVVFS TIDIPYQRRF QNTIAFVGFV AYAALASQYG
TTILNEGLNL LNIPAVKNLA SLTTVTTLWC LYSAWELRRI NATGTSVIRA WLTILSSTIF
GGPAATLAGT FIWSKVELAK ATSFHPTMQS TDTL
