MFR1_PHOSM
ID MFR1_PHOSM Reviewed; 297 AA.
AC A0A3G1DJG9;
DT 18-SEP-2019, integrated into UniProtKB/Swiss-Prot.
DT 13-FEB-2019, sequence version 1.
DT 25-MAY-2022, entry version 9.
DE RecName: Full=Oxidoreductase R1 {ECO:0000303|PubMed:27056201};
DE EC=1.-.-.- {ECO:0000305|PubMed:27056201};
DE AltName: Full=Squalestatin S1 biosynthesis cluster protein R1 {ECO:0000303|PubMed:27056201};
GN Name=R1 {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], AND FUNCTION.
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).
RN [2]
RP FUNCTION.
RX PubMed=11251290; DOI=10.1016/s1074-5521(00)90064-4;
RA Nicholson T.P., Rudd B.A., Dawson M., Lazarus C.M., Simpson T.J., Cox R.J.;
RT "Design and utility of oligonucleotide gene probes for fungal polyketide
RT synthases.";
RL Chem. Biol. 8:157-178(2001).
RN [3]
RP FUNCTION.
RX PubMed=15489970; DOI=10.1039/b411973h;
RA Cox R.J., Glod F., Hurley D., Lazarus C.M., Nicholson T.P., Rudd B.A.,
RA Simpson T.J., Wilkinson B., Zhang Y.;
RT "Rapid cloning and expression of a fungal polyketide synthase gene involved
RT in squalestatin biosynthesis.";
RL Chem. Commun. (Camb.) 2004:2260-2261(2004).
RN [4]
RP FUNCTION.
RX PubMed=28106181; DOI=10.1039/c6cc10172k;
RA Liddle E., Scott A., Han L.C., Ivison D., Simpson T.J., Willis C.L.,
RA Cox R.J.;
RT "In vitro kinetic study of the squalestatin tetraketide synthase
RT dehydratase reveals the stereochemical course of a fungal highly reducing
RT polyketide synthase.";
RL Chem. Commun. (Camb.) 53:1727-1730(2017).
CC -!- FUNCTION: Oxidoreductase; 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:27056201). 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:27056201). These
CC initial steps feature the priming of an unusual benzoic acid starter
CC unit onto the highly reducing polyketide synthase pks2, followed by
CC oxaloacetate extension and product release to generate a tricarboxylic
CC acid containing product (By similarity). The phenylalanine ammonia
CC lyase (PAL) M7 and the acyl-CoA ligase M9 are involved in transforming
CC phenylalanine into benzoyl-CoA (By similarity). The citrate synthase-
CC like protein R3 is involved in connecting the C-alpha-carbons of the
CC hexaketide chain and oxaloacetate to afford the tricarboxylic acid unit
CC (By similarity). The potential hydrolytic enzymes, M8 and M10, are in
CC close proximity to pks2 and may participate in product release (By
CC similarity). On the other side, the tetraketide arm is synthesized by a
CC the squalestatin tetraketide synthase pks1 and enzymatically esterified
CC to the core in the last biosynthetic step, by the acetyltransferase M4
CC (PubMed:11251290, PubMed:15489970, PubMed:28106181). The biosynthesis
CC of the tetraketide must involve 3 rounds of chain extension
CC (PubMed:11251290, PubMed:15489970, PubMed:28106181). After the first
CC and second rounds methyl-transfer occurs, and in all rounds of
CC extension the ketoreductase and dehydratase are active
CC (PubMed:11251290, PubMed:15489970, PubMed:28106181). The enoyl
CC reductase and C-MeT of pks1 are not active in the final round of
CC extension (PubMed:11251290, PubMed:15489970, PubMed:28106181). The
CC acetyltransferase M4 appears to have a broad substrate selectivity for
CC its acyl CoA substrate, allowing the in vitro synthesis of novel
CC squalestatins (Probable). The biosynthesis of SQS1 requires several
CC oxidative steps likely performed by oxidoreductases M1, R1 and R2
CC (Probable). Finally, in support of the identification of the cluster as
CC 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 (Probable).
CC {ECO:0000250|UniProtKB:A0A345BJP6, ECO:0000269|PubMed:11251290,
CC ECO:0000269|PubMed:15489970, ECO:0000269|PubMed:27056201,
CC ECO:0000269|PubMed:28106181, ECO:0000305|PubMed:27056201}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:27056201}.
CC -!- SIMILARITY: Belongs to the asaB hydroxylase/desaturase family.
CC {ECO:0000305}.
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DR EMBL; KU946987; AMY15069.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A3G1DJG9; -.
DR SMR; A0A3G1DJG9; -.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR044053; AsaB-like.
DR PANTHER; PTHR34598; PTHR34598; 1.
PE 3: Inferred from homology;
KW Oxidoreductase.
FT CHAIN 1..297
FT /note="Oxidoreductase R1"
FT /id="PRO_0000447839"
SQ SEQUENCE 297 AA; 33965 MW; B34B01B0ED498FDC CRC64;
MATAILPSTS GVIGLWDGTT DGKEGFMDYA NGDTNVKQPK EYEIQVHDIR KLDPQPTLLK
NGYELVDIPT VVTDEQFIES GKSDEGNAYI KDVYFAECKR IIEEVSGGVD LIIPVSFRMR
EQKGEKESTT KKLGNIESRY APRPVAHLDR DTPTAITVLE ETVGKEKAQE LLSKHKRWAQ
VNVWRPIGNP ATMWPLCFLN HDRIPTWNYD THVGHVWSLN DPRVSDRGQK TYDCVVKHDD
RYDYHYVSDL RPEECLVFCS FDSIPKYAMP HSAFWDNNVP ADAPNRRSIE VRSLVFF
