ID   ASL2_SARSH              Reviewed;         115 AA.
AC   A0A2U8U2L2;
DT   26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT   12-SEP-2018, sequence version 1.
DT   25-MAY-2022, entry version 8.
DE   RecName: Full=Xenovulene A biosynthesis cluster protein asL2 {ECO:0000303|PubMed:29773797};
GN   Name=asL2 {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: Part of the gene cluster that mediates the biosynthesis of
CC       xenovulene A, an unusual meroterpenoid that has potent inhibitory
CC       effects on the human gamma-aminobutyrate A (GABAA) benzodiazepine
CC       receptor (PubMed:29773797). The first step of xenovulene A biosynthesis
CC       is the biosynthesis of 3-methylorcinaldehyde performed by the non-
CC       reducing polyketide synthase aspks1 (PubMed:17912413, PubMed:29773797,
CC       PubMed:20552126). The salicylate hydroxylase asL1 then catalyzes the
CC       oxidative dearomatization of 3-methylorcinaldehyde to yield a
CC       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}.
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DR   EMBL; MG736817; AWM95788.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A2U8U2L2; -.
DR   SMR; A0A2U8U2L2; -.
DR   InterPro; IPR011008; Dimeric_a/b-barrel.
DR   InterPro; IPR005545; YCII.
DR   Pfam; PF03795; YCII; 1.
DR   SUPFAM; SSF54909; SSF54909; 1.
PE   1: Evidence at protein level;
FT   CHAIN           1..115
FT                   /note="Xenovulene A biosynthesis cluster protein asL2"
FT                   /id="PRO_0000449179"
SQ   SEQUENCE   115 AA;  12582 MW;  AFC61B99F723822B CRC64;
     MAAPSLESNW LVQIPNQSGS HVAQARKDSF AEHMSYNKTH IEAGRMVLAG PLVEALPQDG
     QPPVITGSIM VWKATAGERE MLDKWLSDNP FATSGVWDLT KMECTPFLCG VRKGL