ASR5_SARSH
ID ASR5_SARSH Reviewed; 401 AA.
AC A0A2U8U2M1;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 1.
DT 25-MAY-2022, entry version 9.
DE RecName: Full=Putative hetero-Diels-Alderase asR5 {ECO:0000303|PubMed:29773797};
DE EC=5.5.-.- {ECO:0000269|PubMed:29773797};
DE AltName: Full=Xenovulene A biosynthesis cluster protein R5 {ECO:0000303|PubMed:29773797};
DE Flags: Precursor;
GN Name=asR5 {ECO:0000303|PubMed:29773797};
OS Sarocladium schorii (Acremonium strictum (strain IMI 501407)).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Sarocladiaceae; Sarocladium;
OC unclassified Sarocladium.
OX NCBI_TaxID=2203296;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION, FUNCTION, AND PATHWAY.
RX PubMed=29773797; DOI=10.1038/s41467-018-04364-9;
RA Schor R., Schotte C., Wibberg D., Kalinowski J., Cox R.J.;
RT "Three previously unrecognised classes of biosynthetic enzymes revealed
RT during the production of xenovulene A.";
RL Nat. Commun. 9:1963-1963(2018).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=9262310;
RA Thomas P., Sundaram H., Krishek B.J., Chazot P., Xie X., Bevan P.,
RA Brocchini S.J., Latham C.J., Charlton P., Moore M., Lewis S.J.,
RA Thornton D.M., Stephenson F.A., Smart T.G.;
RT "Regulation of neuronal and recombinant GABA(A) receptor ion channels by
RT xenovulene A, a natural product isolated from Acremonium strictum.";
RL J. Pharmacol. Exp. Ther. 282:513-520(1997).
RN [3]
RP FUNCTION.
RX PubMed=17912413; DOI=10.1039/b708614h;
RA Bailey A.M., Cox R.J., Harley K., Lazarus C.M., Simpson T.J., Skellam E.;
RT "Characterisation of 3-methylorcinaldehyde synthase (MOS) in Acremonium
RT strictum: first observation of a reductive release mechanism during
RT polyketide biosynthesis.";
RL Chem. Commun. (Camb.) 39:4053-4055(2007).
RN [4]
RP FUNCTION.
RX PubMed=20552126; DOI=10.1039/c0cc01162b;
RA Fisch K.M., Skellam E., Ivison D., Cox R.J., Bailey A.M., Lazarus C.M.,
RA Simpson T.J.;
RT "Catalytic role of the C-terminal domains of a fungal non-reducing
RT polyketide synthase.";
RL Chem. Commun. (Camb.) 46:5331-5333(2010).
CC -!- FUNCTION: Putative hetero-Diels-Alderase; part of the gene cluster that
CC mediates the biosynthesis of xenovulene A, an unusual meroterpenoid
CC that has potent inhibitory effects on the human gamma-aminobutyrate A
CC (GABAA) benzodiazepine receptor (PubMed:29773797). The first step of
CC xenovulene A biosynthesis is the biosynthesis of 3-methylorcinaldehyde
CC performed by the non-reducing polyketide synthase aspks1
CC (PubMed:17912413, PubMed:29773797, PubMed:20552126). The salicylate
CC hydroxylase asL1 then catalyzes the oxidative dearomatization of 3-
CC methylorcinaldehyde to yield a dearomatized hydroxycyclohexadione
CC (PubMed:29773797). The 2-oxoglutarate-dependent dioxygenase asL3
CC further catalyzes the oxidative ring expansion to provide the first
CC tropolone metabolite (PubMed:29773797). The cytochrome P450
CC monooxygenase asR2 allows the synthesis of tropolone hemiacetal
CC (PubMed:29773797). In parallel, a previously unrecognised class of
CC terpene cyclase, asR6, produces alpha-humulene from
CC farnesylpyrophosphate (FPP) (PubMed:29773797). The putative Diels-
CC Alderase asR5 probably catalyzes the formation of the tropolone-
CC humulene skeleton by linking humulene and the polyketide moiety
CC (PubMed:29773797). Oxidative-ring contractions catalyzed by asL4 and
CC asL6 then processively remove carbon atoms from the polyketide to yield
CC xenovulene A (PubMed:29773797). {ECO:0000269|PubMed:17912413,
CC ECO:0000269|PubMed:20552126, ECO:0000269|PubMed:29773797}.
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:29773797}.
CC -!- INDUCTION: Expression is significantly up-regulated under xenovulene A
CC producing condition. {ECO:0000269|PubMed:29773797}.
CC -!- BIOTECHNOLOGY: Xenovulene A is a natural product exhibiting little
CC structural resemblance with classical benzodiazepines yet is able to
CC displace high-affinity ligand binding to the benzodiazepine site of the
CC gamma-aminobutyrate A (GABAA) receptor and could be potentially used as
CC an anti-depressant with reduced addictive properties.
CC {ECO:0000269|PubMed:9262310}.
CC -!- SIMILARITY: Belongs to the eupF Diels-Alderase family. {ECO:0000305}.
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DR EMBL; MG736817; AWM95794.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A2U8U2M1; -.
DR SMR; A0A2U8U2M1; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 2.120.10.30; -; 1.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
PE 1: Evidence at protein level;
KW Glycoprotein; Isomerase; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..401
FT /note="Putative hetero-Diels-Alderase asR5"
FT /evidence="ECO:0000255"
FT /id="PRO_5016026768"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 401 AA; 44334 MW; 2A1EC23A036F0A59 CRC64;
MRRSFLISAA LGLSMSTPAL AASIQSVLGY LRPTSHHHAP CADDVVLKQS AGSDSAAPDP
LPSRVVHNWP NGTWIENISV RPNGNLLVSQ STPRGRVWQV KEPWLDEPKV ELAYDFDEWV
DRIIGIGETT PDKYVVVGSR FYSLDPQSSQ VERTFCAMEL DFTKGEKPSA RLVARFPHAN
LLQSVSALPW DRSVVLISDQ YLLHPRADWE DLTPGPGQIW RLDTKTGHHE IVMTNYAEMN
TTYNHGLDVG INGIKIHGDH LYWINMDTGG AYRVRIDKYG YPTPLNAVPE TLGVAEDALW
DDFAMHGTRI GEESDDTTMF ATSIVNLMAI SPENGTIVPL AGVGTSEPMG FPGPTSAQFG
RTEKDSHILY VTGKLFNVPP SIRDVVIQGW VRAIDTTGFH F
