ID   PC14_PENCR              Reviewed;         577 AA.
AC   A0A0E3D8M4;
DT   10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT   24-JUN-2015, sequence version 1.
DT   25-MAY-2022, entry version 15.
DE   RecName: Full=Monooxygenase PC-14 {ECO:0000303|PubMed:26213965};
DE            EC=1.-.-.- {ECO:0000305|PubMed:26213965};
DE   AltName: Full=Penitrem biosynthesis cluster 1 protein PC-14 {ECO:0000303|PubMed:26213965};
GN   Name=PC-14 {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: Monooxygenase; part of the gene cluster that mediates the
CC       biosynthesis of the indole diterpenes penitrems (PubMed:26213965). The
CC       geranylgeranyl diphosphate (GGPP) synthase penG catalyzes the first
CC       step in penitrem biosynthesis via conversion of farnesyl pyrophosphate
CC       and isopentyl pyrophosphate into geranylgeranyl pyrophosphate (GGPP)
CC       (Probable). Condensation of indole-3-glycerol phosphate with GGPP by
CC       the prenyl transferase penC then forms 3-geranylgeranylindole (3-GGI)
CC       (Probable). Epoxidation by the FAD-dependent monooxygenase penM leads
CC       to a epoxidized-GGI that is substrate of the terpene cyclase penB for
CC       cyclization to yield paspaline (Probable). Paspaline is subsequently
CC       converted to 13-desoxypaxilline by the cytochrome P450 monooxygenase
CC       penP, the latter being then converted to paxilline by the cytochrome
CC       P450 monooxygenase penQ (PubMed:26213965). Paxilline is converted to
CC       beta-paxitriol via C-10 ketoreduction by the short-chain dehydrogenase
CC       PC-15 which can be monoprenylated at the C-20 by the indole diterpene
CC       prenyltransferase penD (Probable). A two-step elimination (acetylation
CC       and elimination) process performed by the O-acetyltransferase PC-16 and
CC       the P.simplicissimum ptmI-ortholog not yet identified in P.crustosum,
CC       leads to the production of the prenylated form of penijanthine
CC       (Probable). 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 PC-22 (Probable). A
CC       series of oxidation steps involving 4 cytochrome P450 monooxygenases
CC       (PC-21, PC-05, PC-23, PC-20) and a FAD-dependent monooxygenase (PC-14)
CC       are 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 FMO family. {ECO:0000305}.
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DR   EMBL; KC963408; AGZ20195.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A0E3D8M4; -.
DR   SMR; A0A0E3D8M4; -.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR   GO; GO:0004499; F:N,N-dimethylaniline monooxygenase activity; IEA:InterPro.
DR   GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR   Gene3D; 3.50.50.60; -; 1.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   InterPro; IPR000960; Flavin_mOase.
DR   InterPro; IPR020946; Flavin_mOase-like.
DR   Pfam; PF00743; FMO-like; 2.
DR   PIRSF; PIRSF000332; FMO; 1.
DR   PRINTS; PR00370; FMOXYGENASE.
DR   SUPFAM; SSF51905; SSF51905; 1.
PE   3: Inferred from homology;
KW   FAD; Flavoprotein; Monooxygenase; NADP; Oxidoreductase.
FT   CHAIN           1..577
FT                   /note="Monooxygenase PC-14"
FT                   /id="PRO_0000446590"
SQ   SEQUENCE   577 AA;  64467 MW;  2E76196FA851F2D0 CRC64;
     MKVAVIGGGP SGLVTLKYLL AAHHFQPVDP IEVQLFESED RVGGTFSYRT YDRAELVSSA
     QLTTFSDYRW HDKSVDYLSA VEYVEYLEGY CDRFGLRPHI RLSTQVEKVE RTGKGKHRIT
     VSHKGQTSTW DCDAVAVCSG LHVKPNIPSI PGLDRVPVVF HSSEYKHVRQ LGQNTNVMVL
     GTGETGMDIA YFSVTADSTK STTVCHRNGF VIGPKRLPET KLFGRVTSKT PGKALPVDLS
     RPYLFVNSYV HRKVRGALQT TLSRWAVKAG SWLVTGTTRG FDQWVGSLPK DKYDESHYFY
     CKSTKAMPYI SAPYRSHSWV HRLRSSIVQA VLPDTGSRKI DLAPWPEYID EDGVVHFEKN
     SRPDSKVLLQ ERRFKPDVLV LATGYTQSFP FLGSEYCTPD QADQRGIWRT GDASVGYIGF
     VRPSFGAIPP LAEMQVQVWV LNLINRLPGP LVADDSYRLF SNPSGRIEYG VDHDMFAHRL
     ALDIGSAPSF FQALAHGWQV IVFWAMGGTL NTKFRLVGPW AWSGAPRIIH DELLDTVTGR
     RSTIDLLVAL CIRIFQATSV VSSRPSKGDS EVTENRG