ASL1_SARSH
ID ASL1_SARSH Reviewed; 480 AA.
AC A0A2U8U2L6;
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=Salicylate hydroxylase asL1 {ECO:0000303|PubMed:29773797};
DE EC=1.-.-.- {ECO:0000269|PubMed:29773797};
DE AltName: Full=FAD-dependent monooxygenase asL1 {ECO:0000303|PubMed:29773797};
DE AltName: Full=Xenovulene A biosynthesis cluster protein L1 {ECO:0000303|PubMed:29773797};
GN Name=asL1 {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: Salicylate hydroxylase; 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 -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:A6T923};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:29773797}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
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 paxM FAD-dependent monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; MG736817; AWM95796.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A2U8U2L6; -.
DR SMR; A0A2U8U2L6; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Glycoprotein; Membrane; Monooxygenase; Oxidoreductase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..480
FT /note="Salicylate hydroxylase asL1"
FT /id="PRO_0000449178"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 47..48
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 255..257
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 329
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 339..343
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 168
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 250
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 400
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 464
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 480 AA; 53345 MW; 08888C6C5E5DEFFA CRC64;
MDSPEVYEVV DASPEKPMEI AIVGGGIVGV ILAIGLTRQN IKVRVFEQAA SFREIGAGMA
FNACARNCMD LIDPVITQAL LRCGAVNMSD VDAEDDYLRW IDGYNQHRPE DPSYQRPLSE
IGGAGFRGCR RDQFLEELAK EVPQGAVEFR KRLASLEDNT DNGPVVLNFT DGTRAEVDAV
IGCDGIKSVV RKQMFGTNHP ASNAQYTHKV AYRGLVPMNR AVEVLGPWKA GNFHHHVGPG
AHLTHYPVAN NTVLNVVAFL SDPNPWPDNQ RMEMEGSRED VLTGLKGWHP TVLNLVNLLP
EKLSKWALFD LCEFPAPSYS AGRVCIAGDA AHASSPHHGA SACLGVEDCL CLNVLLAQVR
ETVAANQDPA KNRLALSRAI ETAFKTFDTV RHKRTQWLVN SSRRVCDLYH QPEWADPTRW
AKAETCFEEI RDRSYKIWYF DVDGMVKQTR DEYELRQHGE KLGNGTNGVF SDERHGGYTL
