ID   ADRI_PENRO              Reviewed;         245 AA.
AC   A0A1Y0BRF5;
DT   10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT   30-AUG-2017, sequence version 1.
DT   25-MAY-2022, entry version 9.
DE   RecName: Full=Terpene cyclase adrI {ECO:0000303|PubMed:28529508};
DE            EC=4.2.3.- {ECO:0000305|PubMed:28529508};
DE   AltName: Full=Andrastin A biosynthesis cluster protein I {ECO:0000303|PubMed:28529508};
GN   Name=adrI {ECO:0000303|PubMed:28529508};
OS   Penicillium roqueforti.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=5082;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, FUNCTION, AND DISRUPTION
RP   PHENOTYPE.
RC   STRAIN=CECT 2905;
RX   PubMed=28529508; DOI=10.3389/fmicb.2017.00813;
RA   Rojas-Aedo J.F., Gil-Duran C., Del-Cid A., Valdes N., Alamos P., Vaca I.,
RA   Garcia-Rico R.O., Levican G., Tello M., Chavez R.;
RT   "The biosynthetic gene cluster for andrastin A in Penicillium roqueforti.";
RL   Front. Microbiol. 8:813-813(2017).
CC   -!- FUNCTION: Terpene cyclase; part of the gene cluster that mediates the
CC       biosynthesis of andrastins, meroterpenoid compounds that exhibit
CC       inhibitory activity against ras farnesyltransferase, suggesting that
CC       they could be promising leads for antitumor agents (PubMed:28529508).
CC       The first step of the pathway is the synthesis of 3,5-
CC       dimethylorsellinic acid (DMOA) by the polyketide synthase adrD via
CC       condensation of one acetyl-CoA starter unit with 3 malonyl-CoA units
CC       and 2 methylations (By similarity). DMAO is then converted to farnesyl-
CC       DMAO by the prenyltransferase adrG (By similarity). The
CC       methyltransferase adrK catalyzes the methylation of the carboxyl group
CC       of farnesyl-DMAO to farnesyl-DMAO methyl ester which is further
CC       converted to epoxyfarnesyl-DMAO methyl ester by the FAD-dependent
CC       monooxygenase adrH (By similarity). The terpene cyclase adrI then
CC       catalyzes the carbon skeletal rearrangement to generate the andrastin
CC       E, the first compound in the pathway having the andrastin scaffold,
CC       with the tetracyclic ring system (By similarity). The post-cyclization
CC       tailoring enzymes adrF, adrE, adrJ, and adrA, are involved in the
CC       conversion of andrastin E into andrastin A. The short chain
CC       dehydrogenase adrF is responsible for the oxidation of the C-3 a
CC       hydroxyl group of andrastin E to yield the corresponding ketone,
CC       andrastin D. The ketoreductase adrE stereoselectively reduces the
CC       carbonyl moiety to reverse the stereochemistry of the C-3 position to
CC       yield andrastin F. The acetyltransferase adrJ is the acetyltransferase
CC       that attaches the acetyl group to the C-3 hydroxyl group of andrastin F
CC       to yield andrastin C. Finally, the cytochrome P450 monooxygenase adrA
CC       catalyzes two sequential oxidation reactions of the C-23 methyl group,
CC       to generate the corresponding alcohol andrastin B, and aldehyde
CC       andrastin A (By similarity). {ECO:0000250|UniProtKB:B6HV37,
CC       ECO:0000269|PubMed:28529508}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000269|PubMed:28529508}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC       protein {ECO:0000255}.
CC   -!- DISRUPTION PHENOTYPE: Drastically reduces the production of andrastin
CC       A. {ECO:0000269|PubMed:28529508}.
CC   -!- SIMILARITY: Belongs to the paxB family. {ECO:0000305}.
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DR   EMBL; KY349137; ART41214.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A1Y0BRF5; -.
DR   UniPathway; UPA00213; -.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   InterPro; IPR039020; PaxB-like.
DR   PANTHER; PTHR42038; PTHR42038; 1.
PE   3: Inferred from homology;
KW   Glycoprotein; Lyase; Membrane; Transmembrane; Transmembrane helix.
FT   CHAIN           1..245
FT                   /note="Terpene cyclase adrI"
FT                   /id="PRO_0000446495"
FT   TRANSMEM        20..40
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        53..73
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        76..96
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        112..132
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        141..161
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        171..191
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        209..229
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        164
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   245 AA;  27850 MW;  8FBEB5A84243160D CRC64;
     MEESSLLSAI LDHRDALASV AEFLRILAGI CWTLNYFSML RTSRKDKIPS TGIFPLCNDI
     GWEFIYAFIY PTASAHWEGG VRVWFLVHCI VIIFIIKYAH NEWDHFPLIQ RNLYFLYGVV
     TIGFAIGQYS FAREVGPDLG FFYGGVLCQT LASLGPIAQI LSRNSTRGAS LLTWLLRAIA
     TFGGFIKLTI YYLTGNAAGP WFESPMCKFY IGLTLVLDFT YPICYYVIQR QELANAQKEK
     KEKSK