ID   CLZ17_COCLU             Reviewed;         423 AA.
AC   A0A345BJN4;
DT   02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT   07-NOV-2018, sequence version 1.
DT   03-AUG-2022, entry version 12.
DE   RecName: Full=Citrate synthase-like protein clz17 {ECO:0000303|PubMed:28605916};
DE            EC=2.3.3.- {ECO:0000305|PubMed:28605916};
DE   AltName: Full=Squalestatin S1 biosynthesis cluster protein clz17 {ECO:0000303|PubMed:28605916};
DE   AltName: Full=Zaragozic acid A biosynthesis cluster protein 17 {ECO:0000303|PubMed:28605916};
GN   Name=clz17 {ECO:0000303|PubMed:28605916};
OS   Cochliobolus lunatus (Filamentous fungus) (Curvularia lunata).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC   Pleosporomycetidae; Pleosporales; Pleosporineae; Pleosporaceae; Curvularia.
OX   NCBI_TaxID=5503;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP   PATHWAY.
RC   STRAIN=ATCC 74067;
RX   PubMed=28605916; DOI=10.1021/acs.orglett.7b01534;
RA   Liu N., Hung Y.S., Gao S.S., Hang L., Zou Y., Chooi Y.H., Tang Y.;
RT   "Identification and heterologous production of a benzoyl-primed
RT   tricarboxylic acid polyketide intermediate from the zaragozic acid A
RT   biosynthetic pathway.";
RL   Org. Lett. 19:3560-3563(2017).
CC   -!- FUNCTION: Citrate synthase-like protein; part of the gene cluster that
CC       mediates the biosynthesis of squalestatin S1 (SQS1, also known as
CC       zaragozic acid A), a heavily oxidized fungal polyketide that offers
CC       potent cholesterol lowering activity by targeting squalene synthase
CC       (SS) (PubMed:28605916). SQS1 is composed of a 2,8-
CC       dioxobicyclic[3.2.1]octane-3,4,5-tricarboxyclic acid core that is
CC       connected to two lipophilic polyketide arms (PubMed:28605916). These
CC       initial steps feature the priming of an unusual benzoic acid starter
CC       unit onto the highly reducing polyketide synthase clz14, followed by
CC       oxaloacetate extension and product release to generate a tricarboxylic
CC       acid containing product (PubMed:28605916). The phenylalanine ammonia
CC       lyase (PAL) clz10 and the acyl-CoA ligase clz12 are involved in
CC       transforming phenylalanine into benzoyl-CoA (PubMed:28605916). The
CC       citrate synthase-like protein clz17 is involved in connecting the C-
CC       alpha-carbons of the hexaketide chain and oxaloacetate to afford the
CC       tricarboxylic acid unit (PubMed:28605916). The potential hydrolytic
CC       enzymes, clz11 and clz13, are in close proximity to pks2 and may
CC       participate in product release (PubMed:28605916). On the other side,
CC       the tetraketide arm is synthesized by a the squalestatin tetraketide
CC       synthase clz2 and enzymatically esterified to the core in the last
CC       biosynthetic step, by the acetyltransferase clz6 (By similarity). The
CC       biosynthesis of the tetraketide must involve 3 rounds of chain
CC       extension (By similarity). After the first and second rounds methyl-
CC       transfer occurs, and in all rounds of extension the ketoreductase and
CC       dehydratase are active (By similarity). The enoyl reductase and C-MeT
CC       of clz2 are not active in the final round of extension (By similarity).
CC       The acetyltransferase clz6 appears to have a broad substrate
CC       selectivity for its acyl CoA substrate, allowing the in vitro synthesis
CC       of novel squalestatins (By similarity). The biosynthesis of SQS1
CC       requires several oxidative steps likely performed by oxidoreductases
CC       clz3, clz15 and clz16 (Probable). Finally, in support of the
CC       identification of the cluster as being responsible for SQS1 production,
CC       the cluster contains a gene encoding a putative squalene synthase (SS)
CC       clz20, suggesting a likely mechanism for self-resistance (Probable).
CC       {ECO:0000250|UniProtKB:A0A3G1DJJ8, ECO:0000269|PubMed:28605916,
CC       ECO:0000305|PubMed:28605916}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:28605916}.
CC   -!- SIMILARITY: Belongs to the citrate synthase family. {ECO:0000305}.
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DR   EMBL; MF806532; AXF50647.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A345BJN4; -.
DR   SMR; A0A345BJN4; -.
DR   GO; GO:0046912; F:acyltransferase activity, acyl groups converted into alkyl on transfer; IEA:InterPro.
DR   Gene3D; 1.10.230.10; -; 1.
DR   Gene3D; 1.10.580.10; -; 1.
DR   InterPro; IPR016142; Citrate_synth-like_lrg_a-sub.
DR   InterPro; IPR016143; Citrate_synth-like_sm_a-sub.
DR   InterPro; IPR002020; Citrate_synthase.
DR   InterPro; IPR019810; Citrate_synthase_AS.
DR   InterPro; IPR036969; Citrate_synthase_sf.
DR   PANTHER; PTHR11739; PTHR11739; 1.
DR   Pfam; PF00285; Citrate_synt; 1.
DR   PRINTS; PR00143; CITRTSNTHASE.
DR   SUPFAM; SSF48256; SSF48256; 1.
DR   PROSITE; PS00480; CITRATE_SYNTHASE; 1.
PE   1: Evidence at protein level;
KW   Transferase.
FT   CHAIN           1..423
FT                   /note="Citrate synthase-like protein clz17"
FT                   /id="PRO_0000452638"
FT   ACT_SITE        357
FT                   /evidence="ECO:0000250|UniProtKB:A0A3G1DJJ8"
FT   ACT_SITE        413
FT                   /evidence="ECO:0000250|UniProtKB:A0A3G1DJJ8"
SQ   SEQUENCE   423 AA;  46850 MW;  4521924F2D9F1DAD CRC64;
     MATVNGAVGK PQHISKMIES TKMNGNQAQD AAGRADTPVS SDTPDYLHVF DSRTCNIHHI
     PVSDGFVRGS DLSTIAAPVK GNSGRMQKLA VLDPGFQHTA CKESGITFID GEKGELRYRG
     VRIEDLFHDH DFDSTLHLLL WGRLPTNDEK IAFERRIFEA ATPPQEVCDV IRKLPKNTDF
     ISMFLTGLST YMGADEEMTR SRHQAVMTYH KNMKATDDAI IRCFAYVSAT LATVYCHVKG
     VELHPPKEGL TLVENFLHMI GMEDPDKKVS RTIDRLSINM ADHELSCSTA AFLHVASSLT
     DPMTCLLTAI SAASGPLHGG ALEVCYQGLE LIGSVENVPA YIAAVKAKKF RLFGYGHRVY
     KTQDPRAALT KELMEEHREA IAANPLLQIA VEIDRQANTD PYFVERKLKL NADFYGCFVY
     IAL