ID   MFR7_PHOSM              Reviewed;         244 AA.
AC   A0A3G1DJF7;
DT   18-SEP-2019, integrated into UniProtKB/Swiss-Prot.
DT   13-FEB-2019, sequence version 1.
DT   25-MAY-2022, entry version 7.
DE   RecName: Full=Probable hydrolase R7 {ECO:0000303|PubMed:27056201};
DE            EC=3.1.1.- {ECO:0000305|PubMed:27056201};
DE   AltName: Full=Squalestatin S1 biosynthesis cluster protein R7 {ECO:0000303|PubMed:27056201};
DE   Flags: Precursor;
GN   Name=R7 {ECO:0000303|PubMed:27056201};
OS   Phoma sp. (strain ATCC 20986 / MF5453).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC   Pleosporomycetidae; Pleosporales; Pleosporineae; Didymellaceae; Phoma.
OX   NCBI_TaxID=1828523;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND INDUCTION.
RX   PubMed=27056201; DOI=10.1039/c6cc02130a;
RA   Bonsch B., Belt V., Bartel C., Duensing N., Koziol M., Lazarus C.M.,
RA   Bailey A.M., Simpson T.J., Cox R.J.;
RT   "Identification of genes encoding squalestatin S1 biosynthesis and in vitro
RT   production of new squalestatin analogues.";
RL   Chem. Commun. (Camb.) 52:6777-6780(2016).
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 lead compound for the treatment of hyper-cholesterolemia by
CC       targeting squalene synthase (SS) (PubMed:27056201). Both phenylalanine
CC       and benzoic acid are known precursors of SQS1 and so it is unsurprising
CC       that the cluster also contains genes potentially involved in benzoate
CC       production such as phenyl-alanine ammonia lysase (PAL) M7, which
CC       catalyzes the first step in the degradation of phenylalanine, or the
CC       NADP-dependent dehydrogenase M3 (PubMed:27056201). The cluster contains
CC       two PKS encoding genes. The tetraketide synthase is responsible for the
CC       biosynthesis of the tetraketide sidechain of SQS1 (By similarity). The
CC       biosynthesis must involve 3 rounds of chain extension. After the first
CC       and second rounds methyl-transfer occurs, and in all rounds of
CC       extension the ketoreductase and dehydratase areactive. The enoyl
CC       reductase and C-MeT are not active in the final round of extension (By
CC       similarity). The other PKS is therefore likely to encode squalestatin
CC       hexaketide synthase (SQHKS) (PubMed:27056201). The hexaketide main
CC       chain is initiated by benzoate which is an unusual starter unit for a
CC       highly reducing polyketide synthase (PubMed:27056201). The cluster also
CC       contains a gene encoding a citrate synthase-like protein R3 presumably
CC       involved in linking the hexaketide to the oxaloacetate moiety
CC       (Probable). Formation of the tetraketide CoA may be catalyzed by the M9
CC       CoA ligase, but the mechanism of release of the tetraketide and the
CC       hexaketide from their respective PKS remains unknown, although the
CC       cluster encodes a potential esterase (M8) and a possible hydrolase
CC       (M10) which could be involved in these processes (Probable). Two
CC       acyltransferases (AT), M4 and R4, are also encoded in the cluster. M4
CC       is responsible for loading of the tetraketide sidechain from CoA onto
CC       the squalestatin core as the final step of biosynthesis
CC       (PubMed:27056201). M4 appears to have a broad substrate selectivity for
CC       its acyl CoA substrate, allowing the in vitro synthesis of novel
CC       squalestatins (PubMed:27056201). The biosynthesis of SQS1 requires
CC       several oxidative steps likely performed by oxidoreductases M1, R1 and
CC       R2 (Probable). Finally, in support of the identification of the cluster
CC       as being responsible for SQS1 production, the cluster contains a gene
CC       encoding a putative squalene synthase (SS) R6, suggesting a likely
CC       mechanism for self-resistance (PubMed:27056201).
CC       {ECO:0000250|UniProtKB:Q86ZD9, ECO:0000269|PubMed:27056201,
CC       ECO:0000305|PubMed:27056201}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:27056201}.
CC   -!- INDUCTION: Expression is induced on squalestatin S1-producing YMG
CC       medium. {ECO:0000269|PubMed:27056201}.
CC   -!- SIMILARITY: Belongs to the AB hydrolase superfamily. {ECO:0000305}.
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DR   EMBL; KU946987; AMY15075.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A3G1DJF7; -.
DR   SMR; A0A3G1DJF7; -.
DR   GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.1820; -; 1.
DR   InterPro; IPR029058; AB_hydrolase.
DR   InterPro; IPR000073; AB_hydrolase_1.
DR   Pfam; PF12697; Abhydrolase_6; 1.
DR   SUPFAM; SSF53474; SSF53474; 1.
PE   2: Evidence at transcript level;
KW   Glycoprotein; Hydrolase; Signal.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..244
FT                   /note="Probable hydrolase R7"
FT                   /id="PRO_0000447844"
FT   ACT_SITE        192
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250|UniProtKB:Q53547"
FT   ACT_SITE        224
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250|UniProtKB:Q53547"
FT   CARBOHYD        227
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   244 AA;  26235 MW;  1AA63BD64E861694 CRC64;
     MTKPFILLVP GSFAPETIYA STIAHLRTLG FPAVALRLPT TTKRMPLPAA TMAEDADVIK
     RSVEAVLATG QEVVVVCHSY GGTPTTQALG ELGEKKGVRR VVYLSAIIPR VGESNNDAMG
     GKKGELAFEM TEGYMHIDAT TFAPAVCNDL SWDLAYEHTL NLAHHSGASF LEPATQAGYL
     DIPVSYIFCE KDMVVTPEKQ SGFIDVVKEA TGKEVHVVKL DAGHCPNWSM PEKLGDVIAE
     MAGM