CLZ18_COCLU
ID CLZ18_COCLU Reviewed; 469 AA.
AC A0A345BJP8;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 07-NOV-2018, sequence version 1.
DT 25-MAY-2022, entry version 10.
DE RecName: Full=Acyltransferase clz18 {ECO:0000303|PubMed:28605916};
DE Short=AT clz18 {ECO:0000303|PubMed:28605916};
DE EC=2.3.1.- {ECO:0000305|PubMed:28605916};
DE AltName: Full=Squalestatin S1 biosynthesis cluster protein clz18 {ECO:0000303|PubMed:28605916};
DE AltName: Full=Zaragozic acid A biosynthesis cluster protein 18 {ECO:0000303|PubMed:28605916};
GN Name=clz18 {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: Acyltransferase; part of the gene cluster that mediates the
CC biosynthesis of squalestatin S1 (SQS1, also known as zaragozic acid A),
CC a heavily oxidized fungal polyketide that offers potent cholesterol
CC lowering activity by targeting squalene synthase (SS)
CC (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:A0A3G1DJH6, ECO:0000269|PubMed:28605916,
CC ECO:0000305|PubMed:28605916}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:28605916}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the acyltransferase 3 family. {ECO:0000305}.
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DR EMBL; MF806533; AXF50661.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A345BJP8; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016747; F:acyltransferase activity, transferring groups other than amino-acyl groups; IEA:InterPro.
DR InterPro; IPR002656; Acyl_transf_3_dom.
DR Pfam; PF01757; Acyl_transf_3; 1.
PE 3: Inferred from homology;
KW Acyltransferase; Membrane; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..469
FT /note="Acyltransferase clz18"
FT /id="PRO_0000452639"
FT TRANSMEM 21..41
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 70..90
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 134..154
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 253..273
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 346..366
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 391..411
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 424..444
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 469 AA; 52739 MW; 697BDCDFDC180DF3 CRC64;
MIHKPIPNSK PLTAYIDGLR GLLSIIIFNA HLTPVIILGY DKVSRSQVST SPRNVLDIPL
VASCVNNWVL FTIPILKLVY SASPAVCLFF AISGYVMSLK WVRYMNHRSQ TSEINSARIF
TDFGSSIFRR TLRLSLLAMA SMIVPFALMK TGFFDRTVVQ QHGLTKLERG MRFWLEQWEQ
FPARHESWWE QTCDLVQNCA RIFTVFMQRR DEAFSPRYNP VLWTIKADLR ASLALTVTHL
ALLGTKRSSR LQILAALAVL GVAVGSLECP LFWAGWIIAE IHHAAEQTPL AQGKGTGQPR
QKTNTAGMDT FGKTVVLALG CYVASYPTWK PEKAPMFNTF HMMTPGLIVP PRTWHSLGAV
LVLYSLRDVP LARRICESSV AQFLGTHSFA IYLIHFCLVI SFGPDLFSWV WSRTGHENLQ
SLAVGFGITY SILFMAVLLT AAIFRRFIES PVNKCVDSLY RSASVRKEA
