ID LOVF_ASPTE Reviewed; 2532 AA.
AC Q9Y7D5;
DT 03-SEP-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 27-NOV-2024, entry version 135.
DE RecName: Full=Lovastatin diketide synthase lovF {ECO:0000303|PubMed:10334994};
DE Short=LDKS {ECO:0000303|PubMed:10334994};
DE EC=2.3.1.244 {ECO:0000269|PubMed:19530726, ECO:0000269|PubMed:21069965};
DE AltName: Full=Lovastatin biosynthesis cluster protein F {ECO:0000303|PubMed:10334994};
GN Name=lovF {ECO:0000303|PubMed:10334994};
OS Aspergillus terreus.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=33178;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP PATHWAY.
RC STRAIN=ATCC 20542 / MF4845;
RX PubMed=10334994; DOI=10.1126/science.284.5418.1368;
RA Kennedy J., Auclair K., Kendrew S.G., Park C., Vederas J.C.,
RA Hutchinson C.R.;
RT "Modulation of polyketide synthase activity by accessory proteins during
RT lovastatin biosynthesis.";
RL Science 284:1368-1372(1999).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=6933445; DOI=10.1073/pnas.77.7.3957;
RA Alberts A.W., Chen J., Kuron G., Hunt V., Huff J., Hoffman C., Rothrock J.,
RA Lopez M., Joshua H., Harris E., Patchett A., Monaghan R., Currie S.,
RA Stapley E., Albers-Schonberg G., Hensens O., Hirshfield J., Hoogsteen K.,
RA Liesch J., Springer J.;
RT "Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-
RT coenzyme A reductase and a cholesterol-lowering agent.";
RL Proc. Natl. Acad. Sci. U.S.A. 77:3957-3961(1980).
RN [3]
RP FUNCTION.
RX PubMed=10381407; DOI=10.1016/s1074-5521(99)80061-1;
RA Hendrickson L., Davis C.R., Roach C., Nguyen D.K., Aldrich T., McAda P.C.,
RA Reeves C.D.;
RT "Lovastatin biosynthesis in Aspergillus terreus: characterization of
RT blocked mutants, enzyme activities and a multifunctional polyketide
RT synthase gene.";
RL Chem. Biol. 6:429-439(1999).
RN [4]
RP FUNCTION.
RX PubMed=12929390; DOI=10.1039/b207721c;
RA Sorensen J.L., Auclair K., Kennedy J., Hutchinson C.R., Vederas J.C.;
RT "Transformations of cyclic nonaketides by Aspergillus terreus mutants
RT blocked for lovastatin biosynthesis at the lovA and lovC genes.";
RL Org. Biomol. Chem. 1:50-59(2003).
RN [5]
RP FUNCTION.
RX PubMed=17113998; DOI=10.1016/j.chembiol.2006.09.008;
RA Xie X., Watanabe K., Wojcicki W.A., Wang C.C., Tang Y.;
RT "Biosynthesis of lovastatin analogs with a broadly specific
RT acyltransferase.";
RL Chem. Biol. 13:1161-1169(2006).
RN [6]
RP FUNCTION.
RX PubMed=18988191; DOI=10.1002/bit.22028;
RA Xie X., Pashkov I., Gao X., Guerrero J.L., Yeates T.O., Tang Y.;
RT "Rational improvement of simvastatin synthase solubility in Escherichia
RT coli leads to higher whole-cell biocatalytic activity.";
RL Biotechnol. Bioeng. 102:20-28(2009).
RN [7]
RP FUNCTION.
RX PubMed=19875080; DOI=10.1016/j.chembiol.2009.09.017;
RA Gao X., Xie X., Pashkov I., Sawaya M.R., Laidman J., Zhang W., Cacho R.,
RA Yeates T.O., Tang Y.;
RT "Directed evolution and structural characterization of a simvastatin
RT synthase.";
RL Chem. Biol. 16:1064-1074(2009).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH LOVD, COFACTOR,
RP IDENTIFICATION BY MASS SPECTROMETRY, PATHWAY, DOMAIN, AND BIOTECHNOLOGY.
RX PubMed=19530726; DOI=10.1021/ja903203g;
RA Xie X., Meehan M.J., Xu W., Dorrestein P.C., Tang Y.;
RT "Acyltransferase mediated polyketide release from a fungal megasynthase.";
RL J. Am. Chem. Soc. 131:8388-8389(2009).
RN [9]
RP FUNCTION.
RX PubMed=19900898; DOI=10.1126/science.1175602;
RA Ma S.M., Li J.W., Choi J.W., Zhou H., Lee K.K., Moorthie V.A., Xie X.,
RA Kealey J.T., Da Silva N.A., Vederas J.C., Tang Y.;
RT "Complete reconstitution of a highly reducing iterative polyketide
RT synthase.";
RL Science 326:589-592(2009).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, COFACTOR, PHOSPHOPANTETHEINE AT
RP SER-2490, DOMAIN, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=21069965; DOI=10.1021/bi1014776;
RA Meehan M.J., Xie X., Zhao X., Xu W., Tang Y., Dorrestein P.C.;
RT "FT-ICR-MS characterization of intermediates in the biosynthesis of the
RT alpha-methylbutyrate side chain of lovastatin by the 277 kDa polyketide
RT synthase LovF.";
RL Biochemistry 50:287-299(2011).
RN [11]
RP FUNCTION.
RX PubMed=21495633; DOI=10.1021/ja201138v;
RA Barriuso J., Nguyen D.T., Li J.W., Roberts J.N., MacNevin G., Chaytor J.L.,
RA Marcus S.L., Vederas J.C., Ro D.K.;
RT "Double oxidation of the cyclic nonaketide dihydromonacolin L to monacolin
RT J by a single cytochrome P450 monooxygenase, LovA.";
RL J. Am. Chem. Soc. 133:8078-8081(2011).
RN [12]
RP FUNCTION.
RX PubMed=22733743; DOI=10.1073/pnas.1113029109;
RA Ames B.D., Nguyen C., Bruegger J., Smith P., Xu W., Ma S., Wong E.,
RA Wong S., Xie X., Li J.W., Vederas J.C., Tang Y., Tsai S.C.;
RT "Crystal structure and biochemical studies of the trans-acting polyketide
RT enoyl reductase LovC from lovastatin biosynthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:11144-11149(2012).
RN [13]
RP FUNCTION.
RX PubMed=23653178; DOI=10.1002/anie.201302406;
RA Xu W., Chooi Y.H., Choi J.W., Li S., Vederas J.C., Da Silva N.A., Tang Y.;
RT "LovG: the thioesterase required for dihydromonacolin L release and
RT lovastatin nonaketide synthase turnover in lovastatin biosynthesis.";
RL Angew. Chem. Int. Ed. Engl. 52:6472-6475(2013).
RN [14]
RP FUNCTION.
RX PubMed=24727900; DOI=10.1038/nchembio.1503;
RA Jimenez-Oses G., Osuna S., Gao X., Sawaya M.R., Gilson L., Collier S.J.,
RA Huisman G.W., Yeates T.O., Tang Y., Houk K.N.;
RT "The role of distant mutations and allosteric regulation on LovD active
RT site dynamics.";
RL Nat. Chem. Biol. 10:431-436(2014).
RN [15]
RP BIOTECHNOLOGY.
RX PubMed=29236027; DOI=10.3390/ijms18122690;
RA Chen M.C., Tsai Y.C., Tseng J.H., Liou J.J., Horng S., Wen H.C., Fan Y.C.,
RA Zhong W.B., Hsu S.P.;
RT "Simvastatin inhibits cell proliferation and migration in human anaplastic
RT thyroid cancer.";
RL Int. J. Mol. Sci. 18:0-0(2017).
RN [16]
RP BIOTECHNOLOGY.
RX PubMed=29932104; DOI=10.3390/ijms19071834;
RA Zhong W.B., Tsai Y.C., Chin L.H., Tseng J.H., Tang L.W., Horng S.,
RA Fan Y.C., Hsu S.P.;
RT "A synergistic anti-cancer effect of troglitazone and lovastatin in a human
RT anaplastic thyroid cancer cell line and in a mouse xenograft model.";
RL Int. J. Mol. Sci. 19:0-0(2018).
CC -!- FUNCTION: Lovastatin diketide synthase; part of the gene cluster that
CC mediates the biosynthesis of lovastatin (also known as mevinolin,
CC mevacor or monacolin K), a hypolipidemic inhibitor of (3S)-
CC hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR)
CC (PubMed:10334994, PubMed:12929390, PubMed:21495633). The first step in
CC the biosynthesis of lovastatin is the production of dihydromonacolin L
CC acid by the lovastatin nonaketide synthase lovB and the trans-acting
CC enoyl reductase lovC via condensation of one acetyl-CoA unit and 8
CC malonyl-CoA units (PubMed:10334994, PubMed:10381407, PubMed:19900898,
CC PubMed:22733743). Dihydromonacolin L acid is released from lovB by the
CC thioesterase lovG (PubMed:23653178). Next, dihydromonacolin L acid is
CC oxidized by the dihydromonacolin L monooxygenase lovA twice to form
CC monacolin J acid (PubMed:12929390, PubMed:21495633). The 2-
CC methylbutyrate moiety of lovastatin is synthesized by the lovastatin
CC diketide synthase lovF via condensation of one acetyl-CoA unit and one
CC malonyl-CoA unit (PubMed:19530726, PubMed:21069965). Finally, the
CC covalent attachment of this moiety to monacolin J acid is catalyzed by
CC the transesterase lovD to yield lovastatin (PubMed:10334994,
CC PubMed:17113998, PubMed:18988191, PubMed:19875080, PubMed:24727900).
CC LovD has broad substrate specificity and can also convert monacolin J
CC to simvastatin using alpha-dimethylbutanoyl-S-methyl-3-
CC mercaptopropionate (DMB-S-MMP) as the thioester acyl donor, and can
CC also catalyze the reverse reaction and function as hydrolase in vitro
CC (PubMed:19875080). LovD has much higher activity with LovF-bound 2-
CC methylbutanoate than with free diketide substrates (PubMed:21069965).
CC {ECO:0000269|PubMed:10334994, ECO:0000269|PubMed:10381407,
CC ECO:0000269|PubMed:12929390, ECO:0000269|PubMed:17113998,
CC ECO:0000269|PubMed:18988191, ECO:0000269|PubMed:19530726,
CC ECO:0000269|PubMed:19875080, ECO:0000269|PubMed:19900898,
CC ECO:0000269|PubMed:21069965, ECO:0000269|PubMed:21495633,
CC ECO:0000269|PubMed:22733743, ECO:0000269|PubMed:23653178,
CC ECO:0000269|PubMed:24727900}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=holo-[2-methylbutanoate polyketide synthase] + 2 malonyl-CoA +
CC S-adenosyl-L-methionine + 2 NADPH + 3 H(+) = (S)-2-methylbutanoyl-[2-
CC methylbutanoate polyketide synthase] + S-adenosyl-L-homocysteine + 2
CC CO2 + 2 NADP(+) + 2 CoA + H2O; Xref=Rhea:RHEA:42852, Rhea:RHEA-
CC COMP:10260, Rhea:RHEA-COMP:10261, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:57783, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:59789, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:82764; EC=2.3.1.244;
CC Evidence={ECO:0000269|PubMed:19530726, ECO:0000269|PubMed:21069965};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000269|PubMed:19530726, ECO:0000269|PubMed:21069965};
CC Note=Binds 1 phosphopantetheine covalently.
CC {ECO:0000269|PubMed:19530726, ECO:0000269|PubMed:21069965};
CC -!- PATHWAY: Polyketide biosynthesis; lovastatin biosynthesis.
CC {ECO:0000269|PubMed:10334994, ECO:0000269|PubMed:19530726,
CC ECO:0000269|PubMed:21069965}.
CC -!- SUBUNIT: Interacts with LovD. {ECO:0000269|PubMed:19530726}.
CC -!- DOMAIN: Multidomain protein; including a ketosynthase (KS) that
CC catalyzes repeated decarboxylative condensation to elongate the
CC polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects
CC and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain
CC that reduces hydroxyl groups to enoyl groups; a methyltransferase
CC (CMeT) domain responsible for the incorporation of methyl groups; an
CC enoylreductase (ER) domain that reduces enoyl groups to alkyl group; a
CC ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and
CC an acyl-carrier protein (ACP) that serves as the tether of the growing
CC and completed polyketide via its phosphopantetheinyl arm.
CC {ECO:0000305|PubMed:19530726, ECO:0000305|PubMed:21069965}.
CC -!- DISRUPTION PHENOTYPE: Loss of lovastatin biosynthesis.
CC {ECO:0000269|PubMed:10334994}.
CC -!- BIOTECHNOLOGY: Lovastatin acts as a hypolipidemic agent that works as
CC inhibitor of (3S)-hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase
CC (HMGR) which reduces HMG-CoA to mevalonate and is the key step in
CC cholesterol biosynthesis (PubMed:6933445). Lovastatin, simvastatin and
CC related compounds are widely used to treat hypercholesteremia and
CC reduce the risk of cardiovascular disease (PubMed:6933445).
CC Furthermore, statins such as lovastatin were found to be anticancer
CC agents (PubMed:29236027, PubMed:29932104).
CC {ECO:0000269|PubMed:29236027, ECO:0000269|PubMed:29932104,
CC ECO:0000269|PubMed:6933445}.
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DR EMBL; AH007774; AAD34559.1; -; Genomic_DNA.
DR AlphaFoldDB; Q9Y7D5; -.
DR SMR; Q9Y7D5; -.
DR KEGG; ag:AAD34559; -.
DR VEuPathDB; FungiDB:ATEG_09968; -.
DR BioCyc; MetaCyc:MONOMER-18789; -.
DR BRENDA; 2.3.1.244; 536.
DR UniPathway; UPA00875; -.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0016747; F:acyltransferase activity, transferring groups other than amino-acyl groups; IDA:UniProtKB.
DR GO; GO:0004312; F:fatty acid synthase activity; IEA:TreeGrafter.
DR GO; GO:0016491; F:oxidoreductase activity; IDA:UniProtKB.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0016218; F:polyketide synthase activity; IDA:UniProt.
DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0140735; P:lovastatin biosynthetic process; IDA:GO_Central.
DR GO; GO:2001293; P:malonyl-CoA metabolic process; IDA:UniProtKB.
DR GO; GO:0032259; P:methylation; IDA:UniProtKB.
DR GO; GO:0070995; P:NADPH oxidation; IDA:UniProtKB.
DR GO; GO:0030639; P:polyketide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0046500; P:S-adenosylmethionine metabolic process; IDA:UniProtKB.
DR CDD; cd02440; AdoMet_MTases; 1.
DR CDD; cd05195; enoyl_red; 1.
DR CDD; cd00833; PKS; 1.
DR FunFam; 3.40.50.150:FF:000652; Lovastatin nonaketide synthase, polyketide synthase component; 1.
DR FunFam; 3.40.50.720:FF:000209; Polyketide synthase Pks12; 1.
DR FunFam; 3.40.366.10:FF:000002; Probable polyketide synthase 2; 1.
DR Gene3D; 3.30.70.3290; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 1.10.1200.10; ACP-like; 1.
DR Gene3D; 3.40.366.10; Malonyl-Coenzyme A Acyl Carrier Protein, domain 2; 1.
DR Gene3D; 3.90.180.10; Medium-chain alcohol dehydrogenases, catalytic domain; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR Gene3D; 3.10.129.110; Polyketide synthase dehydratase; 1.
DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase_dom.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR013154; ADH-like_N.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR013217; Methyltransf_12.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020807; PKS_DH.
DR InterPro; IPR049551; PKS_DH_C.
DR InterPro; IPR049552; PKS_DH_N.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR049900; PKS_mFAS_DH.
DR InterPro; IPR050091; PKS_NRPS_Biosynth_Enz.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR PANTHER; PTHR43775:SF29; ASPERFURANONE POLYKETIDE SYNTHASE AFOG-RELATED; 1.
DR PANTHER; PTHR43775; FATTY ACID SYNTHASE; 1.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF13602; ADH_zinc_N_2; 1.
DR Pfam; PF22621; CurL-like_PKS_C; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF21089; PKS_DH_N; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00822; PKS_KR; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; ACP-like; 1.
DR SUPFAM; SSF52151; FabD/lysophospholipase-like; 1.
DR SUPFAM; SSF50129; GroES-like; 1.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 2.
DR SUPFAM; SSF55048; Probable ACP-binding domain of malonyl-CoA ACP transacylase; 1.
DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR SUPFAM; SSF53901; Thiolase-like; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00606; KS3_1; 1.
DR PROSITE; PS52004; KS3_2; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
DR PROSITE; PS52019; PKS_MFAS_DH; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..2532
FT /note="Lovastatin diketide synthase lovF"
FT /id="PRO_0000430268"
FT DOMAIN 10..430
FT /note="Ketosynthase family 3 (KS3)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348,
FT ECO:0000305|PubMed:19530726, ECO:0000305|PubMed:21069965"
FT DOMAIN 941..1251
FT /note="PKS/mFAS DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT DOMAIN 2453..2530
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 545..870
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19530726,
FT ECO:0000305|PubMed:21069965"
FT REGION 941..1246
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19530726,
FT ECO:0000305|PubMed:21069965"
FT REGION 941..1078
FT /note="N-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1075..1094
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1092..1251
FT /note="C-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1423..1607
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19530726,
FT ECO:0000305|PubMed:21069965"
FT REGION 1825..2144
FT /note="Enoylreductase (ER) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19530726,
FT ECO:0000305|PubMed:21069965"
FT REGION 2168..2340
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19530726,
FT ECO:0000305|PubMed:21069965"
FT COMPBIAS 1077..1091
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 183
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 318
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 353
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 635
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 973
FT /note="Proton acceptor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT ACT_SITE 1159
FT /note="Proton donor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT MOD_RES 2490
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2532 AA; 276641 MW; C486622B89D58B2E CRC64;
MTPLDAPGAP APIAMVGMGC RFGGGATDPQ KLWKLLEEGG SAWSKIPPSR FNVGGVYHPN
GQRVGSMHVR GGHFLDEDPA LFDASFFNMS TEVASCMDPQ YRLILEVVYE ALEAAGIPLE
QVSGSKTGVF AGTMYHDYQG SFQRQPEALP RYFITGNAGT MLANRVSHFY DLRGPSVSID
TACSTTLTAL HLAIQSLRAG ESDMAIVAGA NLLLNPDVFT TMSNLGFLSS DGISYSFDSR
ADGYGRGEGV AAIVLKTLPD AVRDGDPIRL IVRETAINQD GRTPAISTPS GEAQECLIQD
CYQKAQLDPK QTSYVEAHGT GTRAGDPLEL AVISAAFPGQ QIQVGSVKAN IGHTEAVSGL
ASLIKVALAV EKGVIPPNAR FLQPSKKLLK DTHIQIPLCS QSWIPTDGVR RASINNFGFG
GANAHAIVEQ YGPFAETSIC PPNGYSGNYD GNLGTDQAHI YVLSAKDENS CMRMVSRLCD
YATHARPADD LQLLANIAYT LGSRRSNFRW KAVCTAHSLT GLAQNLAGEG MRPSKSADQV
RLGWVFTGQG AQWFAMGREL IEMYPVFKEA LLECDGYIKE MGSTWSIIEE LSRPETESRV
DQAEFSLPLS TALQIALVRL LWSWNIQPVA VTSHSSGEAA AAYAIGALTA RSAIGISYIR
GALTARDRLA SVHKGGMLAV GLSRSEVGIY IRQVPLQSEE CLVVGCVNSP SSVTVSGDLS
AIAKLEELLH ADRIFARRLK VTQAFHSSHM NSMTDAFRAG LTELFGADPS DAANASKDVI
YASPRTGARL HDMNRLRDPI HWVECMLHPV EFESAFRRMC LDENDHMPKV DRVIEIGPHG
ALGGPIKQIM QLPELATCDI PYLSCLSRGK SSLSTLRLLA SELIRAGFPV DLNAINFPRG
CEAARVQVLS DLPPYPWNHE TRYWKEPRIS QSARQRKGPV HDLIGLQEPL NLPLARSWHN
VLRVSDLPWL RDHVVGSHIV FPGAGFVCMA VMGISTLCSS DHESDDISYI LRDVNFAQAL
ILPADGEEGI DLRLTICAPD QSLGSQDWQR FLVHSITADK NDWTEHCTGL VRAEMDQPPS
SLSNQQRIDP RPWSRKTAPQ ELWDSLHRVG IRHGPFFRNI TCIESDGRGS WCTFAIADTA
SAMPHAYESQ HIVHPTTLDS AVQAAYTTLP FAGSRIKSAM VPARVGCMKI SSRLADLEAR
DMLRAQAKMH SQSPSALVTD VAVFDEADPV GGPVMELEGL VFQSLGASLG TSDRDSTDPG
NTCSSWHWAP DISLVNPGWL EKTLGTGIQE HEISLILELR RCSVHFIQEA MESLSVGDVE
RLSGHLAKFY AWMQKQLACA QNGELGPESS SWTRDSEQAR CSLRSRVVAG STNGEMICRL
GSVLPAILRR EVDPLEVMMD GHLLSRYYVD ALKWSRSNAQ ASELVRLCCH KNPRARILEI
GGGTGGCTQL VVDSLGPNPP VGRYDFTDVS AGFFEAARKR FAGWQNVMDF RKLDIEDDPE
AQGFVCGSYD VVLACQVLHA TSNMQRTLTN VRKLLKPGGK LILVETTRDE LDLFFTFGLL
PGWWLSEEPE RQSTPSLSPT MWRSMLHTTG FNGVEVEARD CDSHEFYMIS TMMSTAVQAT
PMSCSVKLPE VLLVYVDSST PMSWISDLQG EIRGRNCSVT SLQALRQVPP TEGQICVFLG
EVEHSMLGSV TNDDFTLLTS MLQLAGGTLW VTQGATMKSD DPLKALHLGL LRTMRNESHG
KRFVSLDLDP SRNPWTGDSR DAIVSVLDLI SMSDEKEFDY AERDGVIHVP RAFSDSINGG
EEDGYALEPF QDSQHLLRLD IQTPGLLDSL HFTKRNVDTY EPDKLPDDWV EIEPRAFGLN
FRDIMVAMGQ LESNVMGFEC AGVVTSLSET ARTIAPGLAV GDRVCALMNG HWASRVTTSR
TNVVRIPETL SFPHAASIPL AFTTAYISLY TVARILPGET VLIHAGAGGV GQAAIILAQL
TGAEVFTTAG SETKRNLLID KFHLDPDHVF SSRDSSFVDG IKTRTRGKGV DVVLNSLAGP
LLQKSFDCLA RFGRFVEIGK KDLEQNSRLD MSTFVRNVSF SSVDILYWQQ AKPAEIFQAM
SEVILLWERT AIGLIHPISE YPMSALEKAF RTMQSGQHVG KIVVTVAPDD AVLVRQERMP
LFLKPNVSYL VAGGLGGIGR RICEWLVDRG ARYLIILSRT ARVDPVVTSL QERGCTVSVQ
ACDVADESQL EAALQQCRAE EMPPIRGVIQ GAMVLKDALV SQMTADGFHA ALRPKVQGSW
NLHRIASDVD FFVMLSSLVG VMGGAGQANY AAAGAFQDAL AEHRMAHNQP AVTIDLGMVQ
SIGYVAETDS AVAERLQRIG YQPLHEEEVL DVLEQAISPV CSPAAPTRPA VIVTGINTRP
GPHWAHADWM QEARFAGIKY RDPLRDNHGA LSLTPAEDDN LHARLNRAIS QQESIAVIME
AMSCKLISMF GLTDSEMSAT QTLAGIGVDS LVAIELRNWI TAKFNVDISV FELMEGRTIA
KVAEVVLQRY KA
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