ADRG_PENRW
ID ADRG_PENRW Reviewed; 325 AA.
AC B6HV35;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=Prenytransferase adrG {ECO:0000303|Ref.2};
DE EC=2.5.1.- {ECO:0000305|Ref.2};
DE AltName: Full=Andrastin A biosynthesis cluster protein G {ECO:0000303|Ref.2};
GN Name=adrG {ECO:0000303|Ref.2}; ORFNames=Pc22g22880;
OS Penicillium rubens (strain ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin
OS 54-1255) (Penicillium chrysogenum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium;
OC Penicillium chrysogenum species complex.
OX NCBI_TaxID=500485;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin 54-1255;
RX PubMed=18820685; DOI=10.1038/nbt.1498;
RA van den Berg M.A., Albang R., Albermann K., Badger J.H., Daran J.-M.,
RA Driessen A.J.M., Garcia-Estrada C., Fedorova N.D., Harris D.M.,
RA Heijne W.H.M., Joardar V.S., Kiel J.A.K.W., Kovalchuk A., Martin J.F.,
RA Nierman W.C., Nijland J.G., Pronk J.T., Roubos J.A., van der Klei I.J.,
RA van Peij N.N.M.E., Veenhuis M., von Doehren H., Wagner C., Wortman J.R.,
RA Bovenberg R.A.L.;
RT "Genome sequencing and analysis of the filamentous fungus Penicillium
RT chrysogenum.";
RL Nat. Biotechnol. 26:1161-1168(2008).
RN [2]
RP IDENTIFICATION, FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX DOI=10.1016/j.tet.2013.07.029;
RA Matsuda Y., Awakawa T., Abe I.;
RT "Reconstituted biosynthesis of fungal meroterpenoid andrastin A.";
RL Tetrahedron 69:8199-8204(2013).
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 (Ref.2). The first
CC step of the pathway is the synthesis of 3,5-dimethylorsellinic acid
CC (DMOA) by the polyketide synthase adrD via condensation of one acetyl-
CC CoA starter unit with 3 malonyl-CoA units and 2 methylations (Ref.2).
CC DMAO is then converted to farnesyl-DMAO by the prenyltransferase adrG
CC (Ref.2). The methyltransferase adrK catalyzes the methylation of the
CC carboxyl group of farnesyl-DMAO to farnesyl-DMAO methyl ester which is
CC further converted to epoxyfarnesyl-DMAO methyl ester by the FAD-
CC dependent monooxygenase adrH (Ref.2). 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 (Ref.2). 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 (Ref.2). {ECO:0000269|Ref.2}.
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; Evidence={ECO:0000305|Ref.2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49633;
CC Evidence={ECO:0000305|Ref.2};
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:0000305|Ref.2}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the UbiA prenyltransferase family.
CC {ECO:0000305}.
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DR EMBL; AM920437; CAP99576.1; -; Genomic_DNA.
DR RefSeq; XP_002566182.1; XM_002566136.1.
DR AlphaFoldDB; B6HV35; -.
DR SMR; B6HV35; -.
DR STRING; 1108849.XP_002566182.1; -.
DR EnsemblFungi; CAP99576; CAP99576; PCH_Pc22g22880.
DR GeneID; 8309014; -.
DR KEGG; pcs:Pc22g22880; -.
DR VEuPathDB; FungiDB:PCH_Pc22g22880; -.
DR eggNOG; KOG1381; Eukaryota.
DR HOGENOM; CLU_034879_2_0_1; -.
DR OMA; QVARCRV; -.
DR OrthoDB; 1343847at2759; -.
DR BioCyc; PCHR:PC22G22880-MON; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000000724; Contig Pc00c22.
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 1: Evidence at protein level;
KW Magnesium; Membrane; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..325
FT /note="Prenytransferase adrG"
FT /id="PRO_0000446484"
FT TRANSMEM 47..67
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 71..91
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 117..137
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 163..183
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 189..209
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 236..256
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 258..278
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 325 AA; 35901 MW; 0E56911BA584180D CRC64;
MTRRNEKEEV PPQGKILDLF HPGIAPYAEL MRIHRLLGFY LNTSPYLVGV AFSASISSTK
IPIAVLLHRA MLLSIWSIFL RSAGCVWDDL IDMDLDSQIS RTKSRPLPRG AVSPSNALLL
TVALFACGGT VLIFLPWACT VDCLIVTFFA LSYPFGKRFT DYPQITLMNI GWAVPMAMHS
LGLDPLSQMT PTVCMFLFIG SVIIMIDVIY SRQDTEEDLK VGVKSMAVRF RDSIQLLSYS
LLCASTGFLA MAGVLTGLGL PFFVLSVGGH FCGFWVLLRA TQVGKSSGVE SYAKYNMPKQ
AFRPRPETSC ATWLLSTSRN EMGRA
