ASL5_SARSH
ID ASL5_SARSH Reviewed; 249 AA.
AC A0A2U8U2K8;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 1.
DT 03-AUG-2022, entry version 11.
DE RecName: Full=Oxidoreductase asL5 {ECO:0000303|PubMed:29773797};
DE EC=1.1.1.- {ECO:0000305|PubMed:29773797};
DE AltName: Full=Xenovulene A biosynthesis cluster protein L5 {ECO:0000303|PubMed:29773797};
GN Name=asL5 {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 DISRUPTION
RP PHENOTYPE.
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: Oxidoreductase; part of the gene cluster that mediates the
CC biosynthesis of xenovulene A, an unusual meroterpenoid that has potent
CC inhibitory effects on the human gamma-aminobutyrate A (GABAA)
CC benzodiazepine receptor (PubMed:29773797). The first step of xenovulene
CC A biosynthesis is the biosynthesis of 3-methylorcinaldehyde performed
CC by the non-reducing polyketide synthase aspks1 (PubMed:17912413,
CC PubMed:29773797, PubMed:20552126). The salicylate hydroxylase asL1 then
CC catalyzes the oxidative dearomatization of 3-methylorcinaldehyde to
CC yield a dearomatized hydroxycyclohexadione (PubMed:29773797). The 2-
CC oxoglutarate-dependent dioxygenase asL3 further catalyzes the oxidative
CC ring expansion to provide the first tropolone metabolite
CC (PubMed:29773797). The cytochrome P450 monooxygenase asR2 allows the
CC synthesis of tropolone hemiacetal (PubMed:29773797). In parallel, a
CC previously unrecognised class of terpene cyclase, asR6, produces alpha-
CC humulene from farnesylpyrophosphate (FPP) (PubMed:29773797). The
CC putative Diels-Alderase asR5 probably catalyzes the formation of the
CC tropolone-humulene skeleton by linking humulene and the polyketide
CC moiety (PubMed:29773797). Oxidative-ring contractions catalyzed by asL4
CC and asL6 then processively remove carbon atoms from the polyketide to
CC yield xenovulene A (PubMed:29773797). {ECO:0000269|PubMed:17912413,
CC ECO:0000269|PubMed:20552126, ECO:0000269|PubMed:29773797}.
CC -!- INDUCTION: Expression is significantly up-regulated under xenovulene A
CC producing condition. {ECO:0000269|PubMed:29773797}.
CC -!- DISRUPTION PHENOTYPE: Does not affect the production of xenovulene A.
CC {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 short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; MG736817; AWM95785.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A2U8U2K8; -.
DR SMR; A0A2U8U2K8; -.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW NAD; NADP; Oxidoreductase.
FT CHAIN 1..249
FT /note="Oxidoreductase asL5"
FT /id="PRO_0000449185"
FT ACT_SITE 155
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 13..21
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 40..41
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 62..64
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
SQ SEQUENCE 249 AA; 25470 MW; 7548F85A1CDA760A CRC64;
MSAIQRLTGK TAVITGGATG IGFAAAKRFI EEGAFVFIFG RRQEKLDAAT AALGPNSRAV
QGSVTELADL DRLYEAVKAE RGSLDIVMAN AGAGMATPLG KITGEQCDIV FGTNLKGTIF
TIQGALPLMA QAGGGSIILT GSSSGTTGAP PLSVYGASKA AIRNLARSWA GTLRDEGIRI
NVLSPASIAT EIAKEALGEQ GMKMFAQQNP LKRMGQPEEV GAVAAFLASS DSSFMTASEV
SVDGGLAQI
