ID MFR2_PHOSM Reviewed; 293 AA. AC A0A3G1DJF4; DT 18-SEP-2019, integrated into UniProtKB/Swiss-Prot. DT 13-FEB-2019, sequence version 1. DT 18-SEP-2019, entry version 3. DE RecName: Full=Oxidoreductase R2 {ECO:0000303|PubMed:27056201}; DE EC=1.-.-.- {ECO:0000305|PubMed:27056201}; DE AltName: Full=Squalestatin S1 biosynthesis cluster protein R2 {ECO:0000303|PubMed:27056201}; GN Name=R2 {ECO:0000303|PubMed:27056201}; OS Phoma sp. (strain ATCC 20986 / MF5453). OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; OC Dothideomycetes; Pleosporomycetidae; Pleosporales; Pleosporineae; OC 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 RT vitro production of new squalestatin analogues."; RL Chem. Commun. (Camb.) 52:6777-6780(2016). CC -!- FUNCTION: Oxidoreductase; part of the gene cluster that mediates CC the biosynthesis of squalestatin S1 (SQS1, also known as zaragozic CC acid A), a lead compound for the treatment of hyper- CC cholesterolemia by targeting squalene synthase (SS) CC (PubMed:27056201). Both phenylalanine and benzoic acid are known CC precursors of SQS1 and so it is unsurprising that the cluster also CC contains genes potentially involved in benzoate production such as CC phenyl-alanine ammonia lysase (PAL) M7, which catalyzes the first CC step in the degradation of phenylalanine, or the NADP-dependent CC dehydrogenase M3 (PubMed:27056201). The cluster contains two PKS CC encoding genes. The tetraketide synthase is responsible for the CC biosynthesis of the tetraketide sidechain of SQS1 (By similarity). CC The biosynthesis must involve 3 rounds of chain extension. After CC the first and second rounds methyl-transfer occurs, and in all CC rounds of extension the ketoreductase and dehydratase areactive. CC The enoyl reductase and C-MeT are not active in the final round of CC extension (By similarity). The other PKS is therefore likely to CC encode squalestatin hexaketide synthase (SQHKS) (PubMed:27056201). CC The hexaketide main chain is initiated by benzoate which is an CC unusual starter unit for a highly reducing polyketide synthase CC (PubMed:27056201). The cluster also contains a gene encoding a CC citrate synthase-like protein R3 presumably involved in linking CC the hexaketide to the oxaloacetate moiety (Probable). Formation of CC the tetraketide CoA may be catalyzed by the M9 CoA ligase, but the CC mechanism of release of the tetraketide and the hexaketide from CC their respective PKS remains unknown, although the cluster encodes CC a potential esterase (M8) and a possible hydrolase (M10) which CC could be involved in these processes (Probable). Two CC acyltransferases (AT), M4 and R4, are also encoded in the cluster. CC M4 is responsible for loading of the tetraketide sidechain from CC CoA onto the squalestatin core as the final step of biosynthesis CC (PubMed:27056201). M4 appears to have a broad substrate CC selectivity for its acyl CoA substrate, allowing the in vitro CC synthesis of novel squalestatins (PubMed:27056201). The CC biosynthesis of SQS1 requires several oxidative steps likely CC performed by oxidoreductases M1, R1 and R2 (Probable). Finally, in CC support of the identification of the cluster as being responsible CC for SQS1 production, the cluster contains a gene encoding a CC putative squalene synthase (SS) R6, suggesting a likely mechanism CC 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 -!- SIMILARITY: Belongs to the asaB hydroxylase/desaturase family. CC {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; KU946987; AMY15070.1; -; Genomic_DNA. PE 3: Inferred from homology; KW Oxidoreductase. FT CHAIN 1 293 Oxidoreductase R2. FT /FTId=PRO_0000447840. SQ SEQUENCE 293 AA; 33777 MW; 098A01059F50319F CRC64; MATATTTLHS TTGTVYVADG TTDGKVGYYN HTDDSTNVIR KPIPIEVEDA RTLSKSPTTK AEGYQLVNFH TKIPEEHFLN SKLPENKELI EEVYFDECRR LVQEVTGAAE AYPYVYRVRN QEQNAKESNK SNFHTDFVPI VHVDRDDVTA PQRLRASLGA EKADMLLSKY KSYGSINVWR PVKNMVQKWP LMLVDHKSIE DWDYSTHMFT LHSSNDERVA TRGAKEHETI LTHDKRYRYI YASDMTPEEA WLFFAFHSDP ALGIPHGAFW DDSTKEEALT RCSIEVRIWV FFD //