ID   PTMB_PENSI              Reviewed;         243 AA.
AC   A0A140JWT2;
DT   10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT   11-MAY-2016, sequence version 1.
DT   25-MAY-2022, entry version 8.
DE   RecName: Full=Terpene cyclase ptmB {ECO:0000303|PubMed:25831977};
DE            EC=4.2.3.- {ECO:0000269|PubMed:25831977};
DE   AltName: Full=Penitrem biosynthesis cluster 1 protein B {ECO:0000303|PubMed:25831977};
GN   Name=ptmB {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, CATALYTIC
RP   ACTIVITY, 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: Terpene cyclase; part of the gene cluster that mediates the
CC       biosynthesis of the indole diterpenes penitrems (PubMed:25831977). The
CC       geranylgeranyl diphosphate (GGPP) synthase ptmG catalyzes the first
CC       step in penitrem biosynthesis via conversion of farnesyl pyrophosphate
CC       and isopentyl pyrophosphate into geranylgeranyl pyrophosphate (GGPP)
CC       (PubMed:25831977). Condensation of indole-3-glycerol phosphate with
CC       GGPP by the prenyl transferase ptmC then forms 3-geranylgeranylindole
CC       (3-GGI) (PubMed:25831977). Epoxidation by the FAD-dependent
CC       monooxygenase ptmM leads to a epoxidized-GGI that is substrate of the
CC       terpene cyclase ptmB for cyclization to yield paspaline
CC       (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   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:25831977}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC       protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the paxB family. {ECO:0000305}.
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DR   EMBL; LC027936; BAU61559.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A140JWT2; -.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR   InterPro; IPR039020; PaxB-like.
DR   PANTHER; PTHR42038; PTHR42038; 1.
PE   1: Evidence at protein level;
KW   Glycoprotein; Lyase; Membrane; Transmembrane; Transmembrane helix.
FT   CHAIN           1..243
FT                   /note="Terpene cyclase ptmB"
FT                   /id="PRO_0000446546"
FT   TRANSMEM        19..39
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        48..68
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        78..98
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        112..132
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        137..157
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        172..194
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        205..225
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        111
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   243 AA;  27122 MW;  1375B0CDEBCACEF0 CRC64;
     MDGFDVSQAP PEYRSVEPIA NLFVLGMGLG WLINYVGMIY QSFKDETYGM AIMPLCCNIA
     WEIVYSLIYP SKSLTEQGVF IAGLTINIGV MYAAIKFAPK EWSHAPLVMR NLSLIFFLAT
     LGFLTGHLAL AAEIGHSLAY SWGAVVCQLL LSVGGLCQLL CRGCTRGASY TLWLSRFLGS
     SCTVGFASLR WMYWPESFSW LNSPLVLWSL ALFLTVDGSY GICYWYVRQY ELSLKEAEGR
     KSK