ADRG_PENRO
ID ADRG_PENRO Reviewed; 316 AA.
AC A0A1Y0BRF7;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2017, sequence version 1.
DT 03-AUG-2022, entry version 10.
DE RecName: Full=Prenytransferase adrG {ECO:0000303|PubMed:28529508};
DE EC=2.5.1.- {ECO:0000305|PubMed:28529508};
DE AltName: Full=Andrastin A biosynthesis cluster protein G {ECO:0000303|PubMed:28529508};
GN Name=adrG {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: Prenytransferase; 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:B6HV35,
CC ECO:0000269|PubMed:28529508}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate + 3,5-dimethylorsellinate = (3R)-
CC 3-farnesyl-6-hydroxy-2,3,5-trimethyl-4-oxocyclohexa-1,5-diene-1-
CC carboxylate + diphosphate + H(+); Xref=Rhea:RHEA:49632,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:131856,
CC ChEBI:CHEBI:131857, ChEBI:CHEBI:175763;
CC Evidence={ECO:0000305|PubMed:28529508};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49633;
CC Evidence={ECO:0000305|PubMed:28529508};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P32378};
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 UbiA prenyltransferase family.
CC {ECO:0000305}.
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DR EMBL; KY349137; ART41212.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1Y0BRF7; -.
DR SMR; A0A1Y0BRF7; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016765; F:transferase activity, transferring alkyl or aryl (other than methyl) groups; IEA:InterPro.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd13959; PT_UbiA_COQ2; 1.
DR Gene3D; 1.10.357.140; -; 1.
DR InterPro; IPR039653; Prenyltransferase.
DR InterPro; IPR000537; UbiA_prenyltransferase.
DR InterPro; IPR044878; UbiA_sf.
DR PANTHER; PTHR11048; PTHR11048; 1.
DR Pfam; PF01040; UbiA; 1.
PE 3: Inferred from homology;
KW Magnesium; Membrane; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..316
FT /note="Prenytransferase adrG"
FT /id="PRO_0000446485"
FT TRANSMEM 36..56
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 60..80
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 131..151
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 163..183
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 191..211
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 247..267
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 294..314
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 316 AA; 35196 MW; 6D104735170F0052 CRC64;
MTRGNEKEEA PPQAKILGSF PTGIAPYAEL MRVHRLLGFY LNTSPYLVGV AFCASISPTK
IPITVLLHRT ILLSIWSIFL RSAGCVWDDL IDMDLDSQIS RTRTRPLPRG AVSPKNAFLL
TVTLFACGGS VLIYLPWPCA VDCLIITFFA LLYPFGKRFT DYPQITLVNI GWAIPMAMHS
LGLDPLSQMK PTVCMFLFIG LVIIMIDVIY SRQDTEEDLK VGVKSMAVRF RESIELLSYS
LLYASTGFLA MAGFFTGLGL SFFVVSVGGH FCGFWVLLKA TRVGNSYGVE SYAKSAFFLA
TLFWLFGFVI EYCLRN
