ID   PTMA_PENSI              Reviewed;         368 AA.
AC   A0A140JWS9;
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 ptmA {ECO:0000250|UniProtKB:A0A455R4Z0};
DE            EC=5.4.99.- {ECO:0000250|UniProtKB:A0A455R4Z0};
DE   AltName: Full=Penitrem biosynthesis cluster 1 protein A {ECO:0000303|PubMed:25831977};
GN   Name=ptmA {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: Part of the gene cluster that mediates the biosynthesis of
CC       the indole diterpenes penitrems (PubMed:25831977). The geranylgeranyl
CC       diphosphate (GGPP) synthase ptmG catalyzes the first step in penitrem
CC       biosynthesis via conversion of farnesyl pyrophosphate and isopentyl
CC       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:0000305|PubMed:25831977}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC       protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the membrane-bound ascI terpene cyclase family.
CC       {ECO:0000305}.
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DR   EMBL; LC027936; BAU61556.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A140JWS9; -.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
PE   3: Inferred from homology;
KW   Glycoprotein; Isomerase; Membrane; Transmembrane; Transmembrane helix.
FT   CHAIN           1..368
FT                   /note="Terpene cyclase ptmA"
FT                   /id="PRO_0000446542"
FT   TRANSMEM        10..30
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        81..101
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        118..138
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        192..212
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        233..253
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        334..354
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        106
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        140
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   368 AA;  40640 MW;  C69773A951BEE1E6 CRC64;
     MSRVIRSILI ILGSVALYTK YYLSFQNGFI DLLSTMGSQG SLAGLQSGLR SHYTGLDPLD
     RFLKACNVFF WPIFHGTSPA LSLYAIAFAG SMIPMWLILL MHTCVNSSIV EIVMINALAG
     LLVQGIGPGV IMCVLLAMRN TSMKEFAVTG IPAVSILGPN DLPLSLVVCY ILPLALSSLP
     APASISVPSK QLFIAIWQGW PLYIALAVGI AHSLRNHYRR NRPQQLFRHA YAFALACSII
     SHVGLLSISF LSVSPQSPFL SLHSADLHPR SLLIPRLPWQ EVKITSLESG VLRFLHWDYS
     ISSTGTLLWC YDVYWKDRMR GRGWIAFFSL SSRLATMSLA FGPCSVALAL YWAALSNNLM
     KSENARKR