TRT7_ASPTN
ID TRT7_ASPTN Reviewed; 286 AA.
AC Q0C8A0;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 51.
DE RecName: Full=Dioxygenase trt7 {ECO:0000303|PubMed:22549923};
DE EC=1.14.11.- {ECO:0000269|PubMed:25671343};
DE AltName: Full=Terretonin synthesis protein 7 {ECO:0000303|PubMed:22549923};
GN Name=trt7 {ECO:0000303|PubMed:22549923}; ORFNames=ATEG_10084;
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.
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.
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, AND CATALYTIC ACTIVITY.
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: Dioxygenase; part of the gene cluster that mediates the
CC biosynthesis of terretonin, a fungal meroterpenoid that acts as a
CC mycotoxin (PubMed:22549923, PubMed:23116177, PubMed:25671343). The
CC first step of the pathway is the synthesis of 3,5-dimethylorsellinic
CC acid (DMOA) by the polyketide synthase trt4 (PubMed:22549923,
CC PubMed:23116177). DMOA is then prenylated into farnesyl-DMOA by the
CC polyprenyl transferase trt2 (PubMed:22549923, PubMed:22782788,
CC PubMed:23116177). Methylation by the methyltransferase trt5 then leads
CC to farnesyl-DMOA methyl ester which is further subject to epoxidation
CC by the FAD-dependent monooxygenase trt8 to yield epoxyfarnesyl-DMOA
CC methyl ester (PubMed:22549923, PubMed:22782788, PubMed:23116177).
CC Cyclization of epoxyfarnesyl-DMOA methyl ester by the terpene cyclase
CC trt1 leads to a tetracycle intermediate which is in turn converted to
CC preterretonin (PubMed:22549923, PubMed:22782788, PubMed:23116177).
CC Dehydrogenase trt9 comes next to transform preterretonin to
CC preterrenoid (PubMed:22549923, PubMed:23116177). The FAD-dependent
CC monooxygenase trt3 is then required for the C-hydroxylation at C16 of
CC preterrenoid to yield terrenoid (PubMed:22549923, PubMed:23116177). The
CC cytochrome P450 trt6 catalyzes three successive oxidations to transform
CC terrenoid into an unstable intermediate, which then undergoes the D-
CC ring expansion and unusual rearrangement of the methoxy group to afford
CC the core skeleton of terretonin (PubMed:25671343, PubMed:28759016).
CC Trt14 catalyzes the D-ring expansion of terretonin involving
CC intramolecular methoxy rearrangement as well as the hydrolysis of the
CC expanded D-ring and the methyl ester moiety (PubMed:25671343,
CC PubMed:28759016). Finally, the nonheme iron-dependent dioxygenase trt7
CC accomplishes the last two oxidation reactions steps to complete the
CC biosynthesis of terretonin (PubMed:25671343). Terretonin C is produced
CC via spontaneous decarboxylation of the terretonin precursor
CC (PubMed:23116177). Another shunt product of the terretonin biosynthesis
CC is dihydrofarnesyl-DMOA, derived from epoxyfarnesyl-DMOA through
CC hydrolysis of the epoxide (PubMed:22549923, PubMed:22782788,
CC PubMed:23116177). {ECO:0000269|PubMed:22549923,
CC ECO:0000269|PubMed:22782788, ECO:0000269|PubMed:23116177,
CC ECO:0000269|PubMed:25671343, ECO:0000269|PubMed:28759016}.
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:Q4WAW9};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:23116177}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q4WAW9}.
CC -!- DISRUPTION PHENOTYPE: Impairs the synthesis of both terretonin and
CC terretonin C (PubMed:23116177). {ECO:0000269|PubMed:23116177}.
CC -!- SIMILARITY: Belongs to the PhyH family. {ECO:0000305}.
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DR EMBL; CH476609; EAU29533.1; -; Genomic_DNA.
DR RefSeq; XP_001209386.1; XM_001209386.1.
DR AlphaFoldDB; Q0C8A0; -.
DR SMR; Q0C8A0; -.
DR STRING; 341663.Q0C8A0; -.
DR EnsemblFungi; EAU29533; EAU29533; ATEG_10084.
DR GeneID; 4319491; -.
DR VEuPathDB; FungiDB:ATEG_10084; -.
DR eggNOG; ENOG502S7ZW; Eukaryota.
DR HOGENOM; CLU_047725_0_1_1; -.
DR OMA; GHNGDYW; -.
DR OrthoDB; 623398at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR008775; Phytyl_CoA_dOase.
DR Pfam; PF05721; PhyH; 1.
PE 1: Evidence at protein level;
KW Dioxygenase; Iron; Metal-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..286
FT /note="Dioxygenase trt7"
FT /id="PRO_0000436596"
FT BINDING 129
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:O14832"
FT BINDING 131
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:O14832"
FT BINDING 206
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:O14832"
SQ SEQUENCE 286 AA; 31887 MW; CEEDA9CBC6449659 CRC64;
MTGQAEAIRR VHPTVSPKQA AQMLQEDGVI ILKSFLAPDV MQRFQAEVDE DVEKTSTGAR
MKAYKLVNDK TKHMADLIVR SEVFRSDILT HPLYHAIADE LFRADYGDHW LNASAVLQLM
PGAPAQQLHR DEEIFAASKF RSPTDPQLSL SCLVALTEFT EENGATRLIP GSHLWDSAHP
APSPDQTVPA IMQPGEAILF LGSLFHGGGE NRTENVRRGL GMSLIPCQFT PYSSHMHVPR
TIIETMTPLA QKLVGWRTVE SHRQYPFWQG GDRRLEDVLG LASREA
