ID   G431_FUSSX              Reviewed;         456 AA.
AC   A0A6S5ZZ88;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   02-DEC-2020, sequence version 1.
DT   23-FEB-2022, entry version 4.
DE   RecName: Full=Hydroxymethylglutaryl coenzyme A synthase {ECO:0000303|PubMed:32139880};
DE            Short=HMG-CoA synthase {ECO:0000303|PubMed:32139880};
DE            EC=2.3.3.10;
DE   AltName: Full=1233A biosynthesis cluster protein g431 {ECO:0000303|PubMed:32139880};
GN   Name=g431 {ECO:0000303|PubMed:32139880};
OS   Fusarium sp.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium.
OX   NCBI_TaxID=29916;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, INDUCTION, AND DISRUPTION
RP   PHENOTYPE.
RC   STRAIN=RK97-94;
RX   PubMed=32139880; DOI=10.1038/s41429-020-0295-4;
RA   Kato S., Motoyama T., Uramoto M., Nogawa T., Kamakura T., Osada H.;
RT   "Induction of secondary metabolite production by hygromycin B and
RT   identification of the 1233A biosynthetic gene cluster with a self-
RT   resistance gene.";
RL   J. Antibiot. 73:475-479(2020).
CC   -!- FUNCTION: HMG-CoA synthase; part of the gene cluster that mediates the
CC       biosynthesis of 1233A, a natural compound known as an inhibitor of HMG-
CC       CoA synthase in the mevalonate pathway and with antibacterial and
CC       antifungal activities (PubMed:32139880). This enzyme condenses acetyl-
CC       CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for
CC       HMG-CoA reductase (By similarity). As part of the 1233A biosynthesis
CC       cluster, is involved in conferring self-resistance to 1233A
CC       (PubMed:32139880). {ECO:0000255|RuleBase:RU364071,
CC       ECO:0000269|PubMed:32139880}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=acetoacetyl-CoA + acetyl-CoA + H2O = (3S)-hydroxy-3-
CC         methylglutaryl-CoA + CoA + H(+); Xref=Rhea:RHEA:10188,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43074,
CC         ChEBI:CHEBI:57286, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288; EC=2.3.3.10;
CC         Evidence={ECO:0000250|UniProtKB:Q4P3F1};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10189;
CC         Evidence={ECO:0000250|UniProtKB:Q4P3F1};
CC   -!- INDUCTION: Expression is increased upon exposure to hygromycin B.
CC       {ECO:0000269|PubMed:32139880}.
CC   -!- DISRUPTION PHENOTYPE: Does not affect the ability to produce 1233A and
CC       1233B but leads to increased sensitivity to 1233A.
CC       {ECO:0000269|PubMed:32139880}.
CC   -!- SIMILARITY: Belongs to the thiolase-like superfamily. HMG-CoA synthase
CC       family. {ECO:0000305}.
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DR   EMBL; LC516401; BBU37366.1; -; Genomic_DNA.
DR   GO; GO:0004421; F:hydroxymethylglutaryl-CoA synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0006084; P:acetyl-CoA metabolic process; IEA:InterPro.
DR   GO; GO:0010142; P:farnesyl diphosphate biosynthetic process, mevalonate pathway; IEA:InterPro.
DR   GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.47.10; -; 1.
DR   InterPro; IPR013746; HMG_CoA_synt_C_dom.
DR   InterPro; IPR013528; HMG_CoA_synth_N.
DR   InterPro; IPR010122; HMG_CoA_synthase_euk.
DR   InterPro; IPR016039; Thiolase-like.
DR   Pfam; PF08540; HMG_CoA_synt_C; 1.
DR   Pfam; PF01154; HMG_CoA_synt_N; 1.
DR   SUPFAM; SSF53901; SSF53901; 2.
DR   TIGRFAMs; TIGR01833; HMG-CoA-S_euk; 1.
PE   2: Evidence at transcript level;
KW   Lipid biosynthesis; Lipid metabolism; Steroid biosynthesis;
KW   Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase.
FT   CHAIN           1..456
FT                   /note="Hydroxymethylglutaryl coenzyme A synthase"
FT                   /id="PRO_0000454630"
FT   ACT_SITE        85
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT   ACT_SITE        119
FT                   /note="Acyl-thioester intermediate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT   ACT_SITE        258
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
SQ   SEQUENCE   456 AA;  50200 MW;  5806C222096133B4 CRC64;
     MTYPQNVGIK AMEIYVPPQC LDQTLFEKHQ GVSAGKYTIG LGLQYMNFCT DREDVCSLAL
     TAVSSLLRKF DIDPKSIGRL EVGTESPIDK AKSVKSVLTT LFEPHGNTSL EGIDTIHACY
     GGTSALFNAV NWVESRSWDG RDAIVVASDI ALYKEDASRP TGGAGCVAML IGPNAVLSLE
     PSLRGVYMTN TFDFYKPDMK VEFPIVNGHE SIACYLGALD ECHKDLLRRT EAAKKQLNGD
     APKTGKKVLD LFDYMAFHTP NCKLVSKSYG RLKYNDCLNS TNAADWEGIP DELRNLSYKD
     SLKDKTLERA LVAATKTEFK MRVEPCIAAP SLCGNMYTAS LYCSLISLIS NIDLASAEGK
     TIGLFSYGSG AASTLFGMRV TGDLTNMVQK IDLMRRLKQR NIQTPEDYEK ACALRLKAYG
     NKSYKPLGDV SSLTPGTYYL KSIDEAYRRT YAIKGQ