ID   ADRB_PENRW              Reviewed;         213 AA.
AC   B6HUQ5;
DT   10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT   16-DEC-2008, sequence version 1.
DT   25-MAY-2022, entry version 28.
DE   RecName: Full=Andrastin A biosynthesis cluster protein B {ECO:0000303|Ref.2};
GN   Name=adrB {ECO:0000303|Ref.2}; ORFNames=Pc22g22830;
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, AND FUNCTION.
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: Part of the gene cluster that mediates the biosynthesis of
CC       andrastins, meroterpenoid compounds that exhibit inhibitory activity
CC       against ras farnesyltransferase, suggesting that they could be
CC       promising leads for antitumor agents (Ref.2). The first step of the
CC       pathway is the synthesis of 3,5-dimethylorsellinic acid (DMOA) by the
CC       polyketide synthase adrD via condensation of one acetyl-CoA starter
CC       unit with 3 malonyl-CoA units and 2 methylations (Ref.2). DMAO is then
CC       converted to farnesyl-DMAO by the prenyltransferase adrG (Ref.2). 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 (Ref.2). The terpene cyclase adrI then catalyzes the
CC       carbon skeletal rearrangement to generate the andrastin E, the first
CC       compound in the pathway having the andrastin scaffold, with the
CC       tetracyclic ring system (Ref.2). The post-cyclization tailoring enzymes
CC       adrF, adrE, adrJ, and adrA, are involved in the conversion of andrastin
CC       E into andrastin A. The short chain dehydrogenase adrF is responsible
CC       for the oxidation of the C-3 a hydroxyl group of andrastin E to yield
CC       the corresponding ketone, andrastin D. The ketoreductase adrE
CC       stereoselectively reduces the carbonyl moiety to reverse the
CC       stereochemistry of the C-3 position to yield andrastin F. The
CC       acetyltransferase adrJ is the acetyltransferase that attaches the
CC       acetyl group to the C-3 hydroxyl group of andrastin F to yield
CC       andrastin C. Finally, the cytochrome P450 monooxygenase adrA catalyzes
CC       two sequential oxidation reactions of the C-23 methyl group, to
CC       generate the corresponding alcohol andrastin B, and aldehyde andrastin
CC       A (Ref.2). {ECO:0000269|Ref.2}.
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DR   EMBL; AM920437; CAP99571.1; -; Genomic_DNA.
DR   RefSeq; XP_002566177.1; XM_002566131.1.
DR   AlphaFoldDB; B6HUQ5; -.
DR   EnsemblFungi; CAP99571; CAP99571; PCH_Pc22g22830.
DR   GeneID; 8309009; -.
DR   KEGG; pcs:Pc22g22830; -.
DR   VEuPathDB; FungiDB:PCH_Pc22g22830; -.
DR   HOGENOM; CLU_1294794_0_0_1; -.
DR   Proteomes; UP000000724; Contig Pc00c22.
PE   4: Predicted;
KW   Reference proteome.
FT   CHAIN           1..213
FT                   /note="Andrastin A biosynthesis cluster protein B"
FT                   /id="PRO_0000446488"
SQ   SEQUENCE   213 AA;  24460 MW;  0287BC547E361F15 CRC64;
     MQGWIVRISH WNTYLPIAGT MQACGDKSSV WKVAIGYNGH PEEATFFNGR RSYAVNNRGA
     KPEKERTLRL NIEITPVESQ GCNQLPTPAT FEFRIPHSHF FNWSVELYFH NAVLPSYRCH
     FCPRPSLVLR THAISAEYSW LAVDITLGLN RHHNIAVEYV KYIKHLEVGK DIICQLLYLS
     GYFLYVVPLS IPTKYSKYVS QCTVDPYREA GGF