ID   CLZ8_COCLU              Reviewed;         261 AA.
AC   A0A345BJN7;
DT   02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT   07-NOV-2018, sequence version 1.
DT   25-MAY-2022, entry version 8.
DE   RecName: Full=Zaragozic acid A biosynthesis cluster protein 8 {ECO:0000303|PubMed:28605916};
DE   AltName: Full=Squalestatin S1 biosynthesis cluster protein clz8 {ECO:0000303|PubMed:28605916};
GN   Name=clz8 {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, AND 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: Part of the gene cluster that mediates the biosynthesis of
CC       squalestatin S1 (SQS1, also known as zaragozic acid A), a heavily
CC       oxidized fungal polyketide that offers potent cholesterol lowering
CC       activity by targeting squalene synthase (SS) (PubMed:28605916). SQS1 is
CC       composed of a 2,8-dioxobicyclic[3.2.1]octane-3,4,5-tricarboxyclic acid
CC       core that is connected to two lipophilic polyketide arms
CC       (PubMed:28605916). These initial steps feature the priming of an
CC       unusual benzoic acid starter unit onto the highly reducing polyketide
CC       synthase clz14, followed by oxaloacetate extension and product release
CC       to generate a tricarboxylic acid containing product (PubMed:28605916).
CC       The phenylalanine ammonia lyase (PAL) clz10 and the acyl-CoA ligase
CC       clz12 are involved in transforming phenylalanine into benzoyl-CoA
CC       (PubMed:28605916). The citrate synthase-like protein clz17 is involved
CC       in connecting the C-alpha-carbons of the hexaketide chain and
CC       oxaloacetate to afford the tricarboxylic acid unit (PubMed:28605916).
CC       The potential hydrolytic enzymes, clz11 and clz13, are in close
CC       proximity to pks2 and may participate in product release
CC       (PubMed:28605916). On the other side, the tetraketide arm is
CC       synthesized by a the squalestatin tetraketide synthase clz2 and
CC       enzymatically esterified to the core in the last biosynthetic step, by
CC       the acetyltransferase clz6 (By similarity). The biosynthesis of the
CC       tetraketide must involve 3 rounds of chain extension (By similarity).
CC       After the first and second rounds methyl-transfer occurs, and in all
CC       rounds of extension the ketoreductase and dehydratase are active (By
CC       similarity). The enoyl reductase and C-MeT of clz2 are not active in
CC       the final round of extension (By similarity). The acetyltransferase
CC       clz6 appears to have a broad substrate selectivity for its acyl CoA
CC       substrate, allowing the in vitro synthesis of novel squalestatins (By
CC       similarity). The biosynthesis of SQS1 requires several oxidative steps
CC       likely performed by oxidoreductases clz3, clz15 and clz16 (Probable).
CC       Finally, in support of the identification of the cluster as being
CC       responsible for SQS1 production, the cluster contains a gene encoding a
CC       putative squalene synthase (SS) clz20, suggesting a likely mechanism
CC       for self-resistance (Probable). {ECO:0000250|UniProtKB:A0A3G1DJH7,
CC       ECO:0000269|PubMed:28605916, ECO:0000305|PubMed:28605916}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:28605916}.
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DR   EMBL; MF806533; AXF50650.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A345BJN7; -.
PE   3: Inferred from homology;
FT   CHAIN           1..261
FT                   /note="Zaragozic acid A biosynthesis cluster protein 8"
FT                   /id="PRO_0000452624"
FT   REGION          242..261
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   261 AA;  30131 MW;  D4243F16639715D5 CRC64;
     MYLEKEQLPY FNEWAECFCQ YLPDFSIRVT SRAEGSHHKI KIRLHFKGQS HFFHVVQDLN
     QMVNEQRHKH KNKSAANSAR VPANAVYIVK LSQIDQHWFL QPPRAKGLLF EQDDDLFWPL
     DPRVIKLKGR PRGATTKSVL RTPKRRRVIR KKVTDITEEE EVVEAPQSSG SLNAATMRLF
     QQVLHQEMTP MQAQVQALQD RIDSSVVNIS DNKKKVEEEG LRSFDDEFFS PKHVQAVQLS
     YGTRSHTPAA TQRRGQGRGC G