TRT2_ASPTN
ID TRT2_ASPTN Reviewed; 342 AA.
AC Q0C8A6;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 61.
DE RecName: Full=Polyprenyl transferase trt2 {ECO:0000305|PubMed:22549923};
DE EC=2.5.1.- {ECO:0000269|PubMed:22549923, ECO:0000269|PubMed:22782788};
DE AltName: Full=Terretonin synthesis protein 2 {ECO:0000303|PubMed:22549923};
GN Name=trt2 {ECO:0000303|PubMed:22549923}; ORFNames=ATEG_10078;
OS Aspergillus terreus (strain NIH 2624 / FGSC A1156).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=341663;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NIH 2624 / FGSC A1156;
RA Birren B.W., Lander E.S., Galagan J.E., Nusbaum C., Devon K., Henn M.,
RA Ma L.-J., Jaffe D.B., Butler J., Alvarez P., Gnerre S., Grabherr M.,
RA Kleber M., Mauceli E.W., Brockman W., Rounsley S., Young S.K., LaButti K.,
RA Pushparaj V., DeCaprio D., Crawford M., Koehrsen M., Engels R.,
RA Montgomery P., Pearson M., Howarth C., Larson L., Luoma S., White J.,
RA Alvarado L., Kodira C.D., Zeng Q., Oleary S., Yandava C., Denning D.W.,
RA Nierman W.C., Milne T., Madden K.;
RT "Annotation of the Aspergillus terreus NIH2624 genome.";
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22549923; DOI=10.1002/cbic.201200124;
RA Itoh T., Tokunaga K., Radhakrishnan E.K., Fujii I., Abe I., Ebizuka Y.,
RA Kushiro T.;
RT "Identification of a key prenyltransferase involved in biosynthesis of the
RT most abundant fungal meroterpenoids derived from 3,5-dimethylorsellinic
RT acid.";
RL ChemBioChem 13:1132-1135(2012).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22782788; DOI=10.1002/cbic.201200369;
RA Matsuda Y., Awakawa T., Itoh T., Wakimoto T., Kushiro T., Fujii I.,
RA Ebizuka Y., Abe I.;
RT "Terretonin biosynthesis requires methylation as essential step for
RT cyclization.";
RL ChemBioChem 13:1738-1741(2012).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23116177; DOI=10.1021/ol302682z;
RA Guo C.J., Knox B.P., Chiang Y.M., Lo H.C., Sanchez J.F., Lee K.H.,
RA Oakley B.R., Bruno K.S., Wang C.C.;
RT "Molecular genetic characterization of a cluster in A. terreus for
RT biosynthesis of the meroterpenoid terretonin.";
RL Org. Lett. 14:5684-5687(2012).
RN [5]
RP FUNCTION.
RX PubMed=25671343; DOI=10.1021/jacs.5b00570;
RA Matsuda Y., Iwabuchi T., Wakimoto T., Awakawa T., Abe I.;
RT "Uncovering the unusual D-ring construction in terretonin biosynthesis by
RT collaboration of a multifunctional cytochrome P450 and a unique
RT isomerase.";
RL J. Am. Chem. Soc. 137:3393-3401(2015).
RN [6]
RP FUNCTION.
RX PubMed=28759016; DOI=10.1038/nchembio.2443;
RA Mori T., Iwabuchi T., Hoshino S., Wang H., Matsuda Y., Abe I.;
RT "Molecular basis for the unusual ring reconstruction in fungal
RT meroterpenoid biogenesis.";
RL Nat. Chem. Biol. 13:1066-1073(2017).
CC -!- FUNCTION: Polyprenyl transferase; part of the gene cluster that
CC mediates the biosynthesis of terretonin, a fungal meroterpenoid that
CC acts as a mycotoxin (PubMed:22549923, PubMed:23116177,
CC PubMed:25671343). The first step of the pathway is the synthesis of
CC 3,5-dimethylorsellinic acid (DMOA) by the polyketide synthase trt4
CC (PubMed:22549923, PubMed:23116177). DMOA is then prenylated into
CC farnesyl-DMOA by the polyprenyl transferase trt2 (PubMed:22549923,
CC PubMed:22782788, PubMed:23116177). Methylation by the methyltransferase
CC trt5 then leads to farnesyl-DMOA methyl ester which is further subject
CC to epoxidation by the FAD-dependent monooxygenase trt8 to yield
CC epoxyfarnesyl-DMOA methyl ester (PubMed:22549923, PubMed:22782788,
CC PubMed:23116177). Cyclization of epoxyfarnesyl-DMOA methyl ester by the
CC terpene cyclase trt1 leads to a tetracycle intermediate which is in
CC turn converted to preterretonin (PubMed:22549923, PubMed:22782788,
CC PubMed:23116177). Dehydrogenase trt9 comes next to transform
CC preterretonin to preterrenoid (PubMed:22549923, PubMed:23116177). The
CC FAD-dependent monooxygenase trt3 is then required for the C-
CC hydroxylation at C16 of preterrenoid to yield terrenoid
CC (PubMed:22549923, PubMed:23116177). The cytochrome P450 trt6 catalyzes
CC three successive oxidations to transform terrenoid into an unstable
CC intermediate, which then undergoes the D-ring expansion and unusual
CC rearrangement of the methoxy group to afford the core skeleton of
CC terretonin (PubMed:25671343, PubMed:28759016). Trt14 catalyzes the D-
CC ring expansion of terretonin involving intramolecular methoxy
CC rearrangement as well as the hydrolysis of the expanded D-ring and the
CC methyl ester moiety (PubMed:25671343, PubMed:28759016). Finally, the
CC nonheme iron-dependent dioxygenase trt7 accomplishes the last two
CC oxidation reactions steps to complete the biosynthesis of terretonin
CC (PubMed:25671343). Terretonin C is produced via spontaneous
CC decarboxylation of the terretonin precursor (PubMed:23116177). Another
CC shunt product of the terretonin biosynthesis is dihydrofarnesyl-DMOA,
CC derived from epoxyfarnesyl-DMOA through hydrolysis of the epoxide
CC (PubMed:22549923, PubMed:22782788, PubMed:23116177).
CC {ECO:0000269|PubMed:22549923, ECO:0000269|PubMed:22782788,
CC ECO:0000269|PubMed:23116177, ECO:0000269|PubMed:25671343,
CC ECO:0000269|PubMed:28759016}.
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:0000269|PubMed:22549923, ECO:0000269|PubMed:22782788};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49633;
CC Evidence={ECO:0000269|PubMed:22549923, ECO:0000269|PubMed:22782788};
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:23116177}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Impairs the synthesis of terretonin but
CC accumulates 3,5-dimethylorsellinic acid (DMOA) (PubMed:23116177).
CC {ECO:0000269|PubMed:23116177}.
CC -!- SIMILARITY: Belongs to the UbiA prenyltransferase family.
CC {ECO:0000305}.
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DR EMBL; CH476609; EAU29527.1; -; Genomic_DNA.
DR RefSeq; XP_001209380.1; XM_001209380.1.
DR AlphaFoldDB; Q0C8A6; -.
DR SMR; Q0C8A6; -.
DR STRING; 341663.Q0C8A6; -.
DR EnsemblFungi; EAU29527; EAU29527; ATEG_10078.
DR GeneID; 4319421; -.
DR VEuPathDB; FungiDB:ATEG_10078; -.
DR eggNOG; KOG1381; Eukaryota.
DR HOGENOM; CLU_034879_2_0_1; -.
DR OMA; QVARCRV; -.
DR OrthoDB; 1343847at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
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; IPR030470; UbiA_prenylTrfase_CS.
DR InterPro; IPR044878; UbiA_sf.
DR PANTHER; PTHR11048; PTHR11048; 1.
DR Pfam; PF01040; UbiA; 1.
DR PROSITE; PS00943; UBIA; 1.
PE 1: Evidence at protein level;
KW Magnesium; Membrane; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..342
FT /note="Polyprenyl transferase trt2"
FT /id="PRO_0000436591"
FT TRANSMEM 71..91
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 95..115
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 141..161
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 163..183
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 187..207
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 216..236
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 261..278
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 282..304
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 319..339
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 342 AA; 37164 MW; D8E9C7DDB0CC1180 CRC64;
MPILAPLGPS PLSEVFTYSN LPSPVEMATG KDYRHSKAGI LSKLPPSIKP YAELLRIHRP
LGYYLNISPY VVGVAYTAAI APVSLPATVL LNRLIILSLW GFLIRSGGCA WNDLIDMDID
RQVSRTKLRP LPRGAISPTS AALLTAIIFG CGGLLLLLLP SQCTVEAGII LFFALLYPFG
KRFSDYPQLI LVNIAWAIPM AMSSLEVDPL DFPYSTLSMC IFIASVIVMI DVVYACQDAE
EDKKIGARSM AVRYSDITDQ LAYGFFFSGA ISLLLGGVLR GLGLPFIVFS VGGHIFGFLR
FLSVTLGEGT KSASVESRAK SSCLLATVFW VLGFFLEYLA RS
