ASL3_SARSH
ID ASL3_SARSH Reviewed; 340 AA.
AC A0A2U8U2L3;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 1.
DT 03-AUG-2022, entry version 12.
DE RecName: Full=2-oxoglutarate-dependent dioxygenase asL3 {ECO:0000303|PubMed:29773797};
DE EC=1.14.-.- {ECO:0000269|PubMed:29773797};
DE AltName: Full=Xenovulene A biosynthesis cluster protein L3 {ECO:0000303|PubMed:29773797};
GN Name=asL3 {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, CATALYTIC ACTIVITY,
RP 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: 2-oxoglutarate-dependent dioxygenase; part of the gene
CC cluster that mediates the biosynthesis of xenovulene A, an unusual
CC meroterpenoid that has potent inhibitory effects on the human gamma-
CC aminobutyrate A (GABAA) benzodiazepine receptor (PubMed:29773797). The
CC first step of xenovulene A biosynthesis is the biosynthesis of 3-
CC methylorcinaldehyde performed by the non-reducing polyketide synthase
CC aspks1 (PubMed:17912413, PubMed:29773797, PubMed:20552126). The
CC salicylate hydroxylase asL1 then catalyzes the oxidative
CC dearomatization of 3-methylorcinaldehyde to yield a dearomatized
CC hydroxycyclohexadione (PubMed:29773797). The 2-oxoglutarate-dependent
CC dioxygenase asL3 further catalyzes the oxidative ring expansion to
CC provide the first tropolone metabolite (PubMed:29773797). The
CC cytochrome P450 monooxygenase asR2 allows the synthesis of tropolone
CC hemiacetal (PubMed:29773797). In parallel, a previously unrecognised
CC class of 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 -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00805};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU00805};
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 iron/ascorbate-dependent oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; MG736817; AWM95787.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A2U8U2L3; -.
DR SMR; A0A2U8U2L3; -.
DR UniPathway; UPA00213; -.
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 Gene3D; 2.60.120.330; -; 1.
DR InterPro; IPR026992; DIOX_N.
DR InterPro; IPR044861; IPNS-like_FE2OG_OXY.
DR InterPro; IPR027443; IPNS-like_sf.
DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase.
DR Pfam; PF03171; 2OG-FeII_Oxy; 1.
DR Pfam; PF14226; DIOX_N; 1.
DR PROSITE; PS51471; FE2OG_OXY; 1.
PE 1: Evidence at protein level;
KW Dioxygenase; Iron; Metal-binding; Oxidoreductase.
FT CHAIN 1..340
FT /note="2-oxoglutarate-dependent dioxygenase asL3"
FT /id="PRO_0000449180"
FT DOMAIN 187..292
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 214
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 216
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 273
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 283
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
SQ SEQUENCE 340 AA; 37710 MW; 21F178174619CEA3 CRC64;
MGSLTDNAAI PTVDISAFLD PNASQEARQD VVNAMSNACH VYGFFNLAGH GIPQETLREA
FELNKMFFAL PEESKKEVLI SKSIGQSFRG YEPPGIQTHH KGLLPDIKET FMVGREVPLD
DPDCGTFSTG PNLWPSSLPK EKFQDRIMAY QGSMLELVKN ILAILAQGLP KEWGCSPTVF
NSLLDKPSIP MRFLHYAPVP SQLEDVRQFG VADHTDFGCV SILLQEPGTS GLEVYYPPSD
SWIPVPVIDD GFVINMGDMM QRYTGGYYRS ARHRVLTNRE KHRHSVAFFL NGNLGLKAKA
LDGSETETVV GDWIRGRLID TMGQTGKLLQ RESPKPVVLP
