ID   PENO_PENCR              Reviewed;         450 AA.
AC   A0A0E3D8N6;
DT   10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT   24-JUN-2015, sequence version 1.
DT   25-MAY-2022, entry version 17.
DE   RecName: Full=FAD-linked oxidoreductase penO {ECO:0000303|PubMed:26213965};
DE            EC=1.1.1.- {ECO:0000305|PubMed:26213965};
DE   AltName: Full=Penitrem biosynthesis cluster protein O {ECO:0000303|PubMed:26213965};
GN   Name=penO {ECO:0000303|PubMed:26213965};
OS   Penicillium crustosum (Blue mold fungus).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=36656;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, FUNCTION, AND PATHWAY.
RC   STRAIN=PN2402;
RX   PubMed=26213965; DOI=10.3390/toxins7082701;
RA   Nicholson M.J., Eaton C.J., Starkel C., Tapper B.A., Cox M.P., Scott B.;
RT   "Molecular cloning and functional analysis of gene clusters for the
RT   biosynthesis of indole-diterpenes in Penicillium crustosum and P.
RT   janthinellum.";
RL   Toxins 7:2701-2722(2015).
CC   -!- FUNCTION: FAD-linked oxidoreductase; part of the gene cluster that
CC       mediates the biosynthesis of the indole diterpenes penitrems
CC       (PubMed:26213965). The geranylgeranyl diphosphate (GGPP) synthase penG
CC       catalyzes the first step in penitrem biosynthesis via conversion of
CC       farnesyl pyrophosphate and isopentyl pyrophosphate into geranylgeranyl
CC       pyrophosphate (GGPP) (Probable). Condensation of indole-3-glycerol
CC       phosphate with GGPP by the prenyl transferase penC then forms 3-
CC       geranylgeranylindole (3-GGI) (Probable). Epoxidation by the FAD-
CC       dependent monooxygenase penM leads to a epoxidized-GGI that is
CC       substrate of the terpene cyclase penB for cyclization to yield
CC       paspaline (Probable). Paspaline is subsequently converted to 13-
CC       desoxypaxilline by the cytochrome P450 monooxygenase penP, the latter
CC       being then converted to paxilline by the cytochrome P450 monooxygenase
CC       penQ (PubMed:26213965). Paxilline is converted to beta-paxitriol via C-
CC       10 ketoreduction by the short-chain dehydrogenase PC-15 which can be
CC       monoprenylated at the C-20 by the indole diterpene prenyltransferase
CC       penD (Probable). A two-step elimination (acetylation and elimination)
CC       process performed by the O-acetyltransferase PC-16 and the
CC       P.simplicissimum ptmI-ortholog not yet identified in P.crustosum, leads
CC       to the production of the prenylated form of penijanthine (Probable).
CC       The FAD-linked oxidoreductase ptmO then converts the prenylated form of
CC       penijanthine into PC-M5 which is in turn transformed into PC-M4 by the
CC       aromatic dimethylallyltransferase PC-22 (Probable). A series of
CC       oxidation steps involving 4 cytochrome P450 monooxygenases (PC-21, PC-
CC       05, PC-23, PC-20) and a FAD-dependent monooxygenase (PC-14) are
CC       required for the transformation of PC-M4 to penitrems A and E.
CC       Synthesis of these final products is proposed to proceed via penitrems
CC       D and C (PC-21, PC-05, PC-14) and penitrems B and F (PC-21, PC-05, PC-
CC       14, PC-23) (Probable). {ECO:0000269|PubMed:26213965,
CC       ECO:0000305|PubMed:26213965}.
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:26213965}.
CC   -!- SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase
CC       family. {ECO:0000305}.
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DR   EMBL; KC963408; AGZ20199.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A0E3D8N6; -.
DR   SMR; A0A0E3D8N6; -.
DR   GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.30.43.10; -; 1.
DR   Gene3D; 3.30.465.10; -; 1.
DR   InterPro; IPR016166; FAD-bd_PCMH.
DR   InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR   InterPro; IPR016167; FAD-bd_PCMH_sub1.
DR   InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR   InterPro; IPR006094; Oxid_FAD_bind_N.
DR   Pfam; PF01565; FAD_binding_4; 1.
DR   SUPFAM; SSF56176; SSF56176; 1.
DR   PROSITE; PS51387; FAD_PCMH; 1.
PE   3: Inferred from homology;
KW   FAD; Flavoprotein; Oxidoreductase.
FT   CHAIN           1..450
FT                   /note="FAD-linked oxidoreductase penO"
FT                   /id="PRO_0000446569"
FT   DOMAIN          32..203
FT                   /note="FAD-binding PCMH-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
SQ   SEQUENCE   450 AA;  50312 MW;  D724005851EBF046 CRC64;
     MKHTLPSALV TLWRDSPGYE SARSRTFNQR VPPELPYAIV KPKNVEQIQQ AVQLAIDLDK
     QIRIRSGGHS LAGWTLCADS ILIDLVDFMH LEYDATTAIA SASPSATSAQ LNDLLVPHGR
     FVPVGHCGDV GLGGFFLQGG MGLNCRSYGW ACEYLVGVDL ITADGEYKHC SESENADLFW
     AARGAGPEFP AIVTRFFIRT RPAAAKHEKS TFIWPVACSD AVVSWILKIL PELHADIEPL
     VVSTIVPGPN IAAILVQFLV FLGTNETGAE KLEPSLTAMP DGTIMEFKGV STSIQQEYVS
     QEGTMPRDSR YICDSVWFKD GIDFVAVTRR MFREFPRDRS MVYWEPKYPT SRRKLPDMAF
     SLQADQYLAL FAIFEDSQQD QEQGIRIQEF IQEIEPYVLG TFAADGVPAV RKTQYWSAEV
     IERLYSVCQK WDPAHRLGCT LLDPTRKMKS