ID   ATNA_ARTSZ              Reviewed;         751 AA.
AC   A0A455LLW3;
DT   02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT   05-JUN-2019, sequence version 1.
DT   03-AUG-2022, entry version 12.
DE   RecName: Full=FAD-dependent monooxygenase atnA {ECO:0000303|PubMed:29797385};
DE            EC=1.-.-.- {ECO:0000305|PubMed:29797385};
DE   AltName: Full=Arthripenoid biosynthesis cluster protein A {ECO:0000303|PubMed:29797385};
GN   Name=atnA {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: FAD-dependent 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=FAD; Xref=ChEBI:CHEBI:57692;
CC         Evidence={ECO:0000250|UniProtKB:A6T923};
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000269|PubMed:29797385}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC       protein {ECO:0000255}.
CC   -!- INDUCTION: Expression is induce on medium.
CC       {ECO:0000269|PubMed:29797385}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of arthripenoids but
CC       leads to the accumulation of a new compound that possesses a
CC       sesquiterpenoid chain with adiol group at C12' and C13' position.
CC       {ECO:0000269|PubMed:29797385}.
CC   -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC       {ECO:0000305}.
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DR   EMBL; MH183007; AYO60874.1; -; mRNA.
DR   AlphaFoldDB; A0A455LLW3; -.
DR   SMR; A0A455LLW3; -.
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; Membrane; Monooxygenase; Oxidoreductase; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..751
FT                   /note="FAD-dependent monooxygenase atnA"
FT                   /id="PRO_0000452553"
FT   TRANSMEM        8..28
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        446..466
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        481..501
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        508..528
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        563..583
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        590..610
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        639..659
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        663..683
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        706..726
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"
SQ   SEQUENCE   751 AA;  82642 MW;  0F68383ED2D46FA1 CRC64;
     MATPFKVLIV GGGVAGLSLA IMLEAYGFDY ELLEKHPDVA PKLGAGVGLT PNGARILDQI
     GVWDSMCEYA SPVDAGIALS PTGNTVIFNP HMGEWLEKLF GYKIHFLSRH DCLRILFDKI
     KQKSNIHLRK EVTRISVGQP GEKAQVETKD GSTYIADLVI GADGVRSSVR NELWRIADTE
     KPGYIPNRDK SGIVSIYTAV IGIAHDPGLP RGGSARAYNH LRSYFTQEGV EGSGVFYWWL
     CTKNEEPIKG IVPKLSSDTK QTLLDKYADD QIGHGLTLGG LYKKSVYSAI IPLQEFVLEK
     CFYKNILLIG DTFRKLHPVA GQGANSAIEE SALVADILWQ LRENNALHDA AGMKQALTEF
     QEERFVRTTA LREDANLVQR MESFDNLFMK FLSLHVIPRL PFVVAFLPQL GSAFTPARCM
     KYLPPPKAGM CPFSPDMQAK PNPRSPLATI SWIVFLTLAA CFPWSVHRLL PASSSSLPGF
     SEVFQLYTSV MAVSISGLWV IESYKASLLI SPMFSSLPWI LASNYWGWDK TLPVYLCFHV
     ISSQHTVHYY TPQFMTDLGA AKALLPCLAM AYSIPGILTA LASTDQTLSD WWPVAHCTFP
     VLVYVSSTFL RGMKAVPQGV EVVFSSVDLP YQRRFLTAIA VVSSAVHVTL IWNHGAALLN
     EGIISLLSVP LARTLASLTA LIVAWGIYMT WEMRRIFATE VSLVKAWAVI LVSTVLLGPA
     ASLAGATYWS KVMLEKATSM QPLVQPTNGK S