ID   PTMO_PENSI              Reviewed;         450 AA.
AC   A0A140JWT7;
DT   10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT   11-MAY-2016, sequence version 1.
DT   25-MAY-2022, entry version 14.
DE   RecName: Full=FAD-linked oxidoreductase ptmO {ECO:0000303|PubMed:25831977};
DE            EC=1.1.1.- {ECO:0000269|PubMed:25831977};
DE   AltName: Full=Penitrem biosynthesis cluster 2 protein O {ECO:0000303|PubMed:25831977};
GN   Name=ptmO {ECO:0000303|PubMed:25831977};
OS   Penicillium simplicissimum.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=69488;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, FUNCTION, AND PATHWAY.
RC   STRAIN=AK-40;
RX   PubMed=25831977; DOI=10.1002/anie.201501072;
RA   Liu C., Tagami K., Minami A., Matsumoto T., Frisvad J.C., Suzuki H.,
RA   Ishikawa J., Gomi K., Oikawa H.;
RT   "Reconstitution of biosynthetic machinery for the synthesis of the highly
RT   elaborated indole diterpene penitrem.";
RL   Angew. Chem. Int. Ed. 54:5748-5752(2015).
CC   -!- FUNCTION: FAD-linked oxidoreductase; part of the gene cluster that
CC       mediates the biosynthesis of the indole diterpenes penitrems
CC       (PubMed:25831977). The geranylgeranyl diphosphate (GGPP) synthase ptmG
CC       catalyzes the first step in penitrem biosynthesis via conversion of
CC       farnesyl pyrophosphate and isopentyl pyrophosphate into geranylgeranyl
CC       pyrophosphate (GGPP) (PubMed:25831977). Condensation of indole-3-
CC       glycerol phosphate with GGPP by the prenyl transferase ptmC then forms
CC       3-geranylgeranylindole (3-GGI) (PubMed:25831977). Epoxidation by the
CC       FAD-dependent monooxygenase ptmM leads to a epoxidized-GGI that is
CC       substrate of the terpene cyclase ptmB for cyclization to yield
CC       paspaline (PubMed:25831977). Paspaline is subsequently converted to 13-
CC       desoxypaxilline by the cytochrome P450 monooxygenase ptmP, the latter
CC       being then converted to paxilline by the cytochrome P450 monooxygenase
CC       ptmQ (PubMed:25831977). Paxilline is converted to beta-paxitriol via C-
CC       10 ketoreduction by the short-chain dehydrogenase ptmH which can be
CC       monoprenylated at the C-20 by the indole diterpene prenyltransferase
CC       ptmD (PubMed:25831977). A two-step elimination (acetylation and
CC       elimination) process performed by the O-acetyltransferase ptmV and ptmI
CC       leads to the production of the prenylated form of penijanthine
CC       (PubMed:25831977). The FAD-linked oxidoreductase ptmO then converts the
CC       prenylated form of penijanthine into PC-M5 which is in turn transformed
CC       into PC-M4 by the aromatic dimethylallyltransferase ptmE
CC       (PubMed:25831977). Five sequential oxidative transformations performed
CC       by the cytochrome P450 monooxygenases ptmK, ptmU, ptmL, ptmN and ptmJ
CC       yield the various penitrem compounds. PtmK, ptmU and ptmM are involved
CC       in the formation of the key bicyclic ring of penitrem C via the
CC       formation of the intermediates secopenitrem D and penitrem D. PtmL
CC       catalyzes the epoxidation of penitrem D and C to yield penitrem B and
CC       F, respectively. PtmJ catalyzes the last benzylic hydroxylation to
CC       convert penitrem B to prenitrem E and penitrem F to penitrem A
CC       (PubMed:25831977). {ECO:0000269|PubMed:25831977}.
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:25831977}.
CC   -!- SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase
CC       family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; LC027937; BAU61564.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A140JWT7; -.
DR   SMR; A0A140JWT7; -.
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 ptmO"
FT                   /id="PRO_0000446570"
FT   DOMAIN          32..203
FT                   /note="FAD-binding PCMH-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
SQ   SEQUENCE   450 AA;  50474 MW;  A113D6830ACBDA71 CRC64;
     MKHNLPADLV TLWRDSPGYE SARSRTFNQR IPPELPYAIV RPKNMEQIQH AVQLAVDLDK
     QIRIRSGGHS LAGWTLCADS ILIDLVDFRH LEYDATTAIA SASPSATSAQ LNDLLVPHGR
     FVPVGHCGDV GLGGFFLQGG MGLNCRSYGW ACEYLVGVDL ITADGEYKHC SESENADLFW
     AARGAGPEFP AIVTRFFIRT RPAAAKYEKS TFIWPVACSD AVVSWILKIL PELHADIEPL
     VVSTIVPGLN VAAILVQFLV FLSTNETGAE KLGPSLTAMP DGTLMEFKGV PTSIQQEYVS
     QEGTMPRDSR YICDSVWFKD GIDFVTVTRR MFREFPRDRS MVYWEPKYPT SRRQLPDMAF
     SLQADQYLAL FAIFEDSQQD EEQGIRIQEF IQEIEPYVLG TFAADGMPAV RKTQYWSAEV
     IERLYSVCQK WDPAHRLGCT LLDPTRKVKS