CLZ13_COCLU
ID CLZ13_COCLU Reviewed; 613 AA.
AC A0A345BJP5;
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=Probable hydrolase clz13 {ECO:0000303|PubMed:28605916};
DE EC=3.5.-.-;
DE AltName: Full=Squalestatin S1 biosynthesis cluster protein clz13 {ECO:0000303|PubMed:28605916};
DE AltName: Full=Zaragozic acid A biosynthesis cluster protein 13 {ECO:0000303|PubMed:28605916};
DE Flags: Precursor;
GN Name=clz13 {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: Probable hydrolase; part of the gene cluster that mediates
CC the biosynthesis of squalestatin S1 (SQS1, also known as zaragozic acid
CC A), 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:A0A3G1DJI3, ECO:0000269|PubMed:28605916,
CC ECO:0000305|PubMed:28605916}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:28605916}.
CC -!- SIMILARITY: Belongs to the beta-lactamase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; MF806533; AXF50658.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A345BJP5; -.
DR SMR; A0A345BJP5; -.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.40.710.10; -; 1.
DR InterPro; IPR001466; Beta-lactam-related.
DR InterPro; IPR012338; Beta-lactam/transpept-like.
DR Pfam; PF00144; Beta-lactamase; 1.
DR SUPFAM; SSF56601; SSF56601; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Hydrolase; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..613
FT /note="Probable hydrolase clz13"
FT /id="PRO_5016566148"
FT CARBOHYD 61
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 286
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 422
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 456
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 477
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 581
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 613 AA; 67239 MW; 54F3657FBB492EAF CRC64;
MCLLSMRFTV AILLVLLSHC GGSHATSCTP GQPFPVPSYP ESSLQETFEH IFETASGYFE
NESFQATNVA IEVTSSRETL WSFYHAAKNQ SSQDGSTVIG KDTVFRVARV SKLLTAIAVL
QLHDQGHVSS LYDPINDYIP DLEPSSVQWD RVTIWDLLNN VAGILDMCSY TLFDKRLNTN
SDFTIDGYAD IYMDFSARQK ADLNLPPVSD AILEVMPACQ VDKSIPCDSA GLLSWLRSSK
AVFNPHQVNS NSNVGFSLLG ILIERISGVK YEQFIHQTII EPLQLNSTSF RPPHKDSGAV
LQNDHTWSWD VGVNNPSVGL YSTPCDISTL LRWTLNKSPS SILNWFAPGF YAVGSHSLIG
MPWNIFRTTT PLSIPNRPTT FNTVVGTLGP YTSVVVVMPE YDLAVSLMMN GALGHPHDIL
TNVTFPLIRA ADKIALESVQ DNYAGTYKAE PGQKINSSIT LSVSSDHGLR ISELISNGSS
ILPVMERLAS SKSGGGANWI FQAVPTFLDS KHQGRRGDGV IVDEEWRWTY VLDKPPGEGW
NDWCLSSFDP VTYAGEPLTK MVFHKDAKSG RVLSVALSGY NITLTKAVQE ADSFAQGDAL
DLLAHAGQEV LAE
