ID LOVB_ASPTN Reviewed; 3038 AA.
AC Q0C8M3;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 2.
DT 27-MAR-2024, entry version 95.
DE RecName: Full=Lovastatin nonaketide synthase, polyketide synthase component;
DE Short=LNKS;
DE EC=2.3.1.161 {ECO:0000250|UniProtKB:Q9Y8A5};
GN Name=lovB; ORFNames=ATEG_09961;
OS Aspergillus terreus (strain NIH 2624 / FGSC A1156).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=341663;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NIH 2624 / FGSC A1156;
RA Birren B.W., Lander E.S., Galagan J.E., Nusbaum C., Devon K., Henn M.,
RA Ma L.-J., Jaffe D.B., Butler J., Alvarez P., Gnerre S., Grabherr M.,
RA Kleber M., Mauceli E.W., Brockman W., Rounsley S., Young S.K., LaButti K.,
RA Pushparaj V., DeCaprio D., Crawford M., Koehrsen M., Engels R.,
RA Montgomery P., Pearson M., Howarth C., Larson L., Luoma S., White J.,
RA Alvarado L., Kodira C.D., Zeng Q., Oleary S., Yandava C., Denning D.W.,
RA Nierman W.C., Milne T., Madden K.;
RT "Annotation of the Aspergillus terreus NIH2624 genome.";
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
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 [3]
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
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 [5]
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 [6]
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 [7]
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 [8]
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 [9]
RP FUNCTION.
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 [10]
RP FUNCTION, PATHWAY, COFACTOR, AND IDENTIFICATION BY MASS SPECTROMETRY.
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 [11]
RP FUNCTION.
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 [12]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
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 [13]
RP FUNCTION, AND INTERACTION WITH LOVC.
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 [14]
RP FUNCTION, CATALYTIC ACTIVITY, AND DOMAIN.
RX PubMed=23023987; DOI=10.1002/cbic.201200449;
RA Boettger D., Bergmann H., Kuehn B., Shelest E., Hertweck C.;
RT "Evolutionary imprint of catalytic domains in fungal PKS-NRPS hybrids.";
RL ChemBioChem 13:2363-2373(2012).
RN [15]
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 [16]
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 [17]
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 [18]
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 nonaketide 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, PubMed:23023987).
CC The first step in the biosynthesis of lovastatin is the production of
CC dihydromonacolin L acid by the lovastatin nonaketide synthase lovB and
CC the trans-acting enoyl reductase lovC via condensation of one acetyl-
CC CoA unit and 8 malonyl-CoA units (PubMed:10334994, PubMed:10381407,
CC PubMed:19900898, PubMed:22733743, PubMed:23023987). Dihydromonacolin L
CC acid is released from lovB by the thioesterase lovG (PubMed:23653178).
CC Next, dihydromonacolin L acid is oxidized by the dihydromonacolin L
CC monooxygenase lovA twice to form monacolin J acid (PubMed:12929390,
CC PubMed:21495633). The 2-methylbutyrate moiety of lovastatin is
CC synthesized by the lovastatin diketide synthase lovF via condensation
CC of one acetyl-CoA unit and one malonyl-CoA unit (PubMed:19530726,
CC PubMed:21069965). Finally, the covalent attachment of this moiety to
CC monacolin J acid is catalyzed by the transesterase lovD to yield
CC lovastatin (PubMed:10334994, PubMed:17113998, PubMed:18988191,
CC PubMed:19875080, PubMed:24727900). LovD has broad substrate specificity
CC and can also convert monacolin J to simvastatin using alpha-
CC dimethylbutanoyl-S-methyl-3-mercaptopropionate (DMB-S-MMP) as the
CC thioester acyl donor, and can also catalyze the reverse reaction and
CC function as hydrolase in vitro (PubMed:19875080). LovD has much higher
CC activity with LovF-bound 2-methylbutanoate than with free diketide
CC substrates (PubMed:21069965). {ECO:0000269|PubMed:10334994,
CC ECO:0000269|PubMed:10381407, ECO:0000269|PubMed:12929390,
CC ECO:0000269|PubMed:17113998, ECO:0000269|PubMed:18988191,
CC ECO:0000269|PubMed:19530726, ECO:0000269|PubMed:19875080,
CC ECO:0000269|PubMed:19900898, ECO:0000269|PubMed:21069965,
CC ECO:0000269|PubMed:21495633, ECO:0000269|PubMed:22733743,
CC ECO:0000269|PubMed:23023987, ECO:0000269|PubMed:23653178,
CC ECO:0000269|PubMed:24727900}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=19 H(+) + holo-[lovastatin nonaketide synthase] + 9 malonyl-
CC CoA + 11 NADPH + S-adenosyl-L-methionine = 9 CO2 + 9 CoA +
CC dihydromonacolin L-[lovastatin nonaketide synthase] + 6 H2O + 11
CC NADP(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:18565, Rhea:RHEA-
CC COMP:10042, Rhea:RHEA-COMP:10043, 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:79032; EC=2.3.1.161;
CC Evidence={ECO:0000269|PubMed:10334994, ECO:0000269|PubMed:10381407,
CC ECO:0000269|PubMed:23023987};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000269|PubMed:19900898};
CC Note=Binds 1 phosphopantetheine covalently.
CC {ECO:0000269|PubMed:19900898};
CC -!- PATHWAY: Polyketide biosynthesis; lovastatin biosynthesis.
CC {ECO:0000269|PubMed:10334994, ECO:0000269|PubMed:10381407,
CC ECO:0000269|PubMed:19900898}.
CC -!- SUBUNIT: Interacts with LovC. {ECO:0000269|PubMed:22733743}.
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; 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 (PubMed:22733743). A C-terminal thioesterase (TE) domain that is often
CC found in polyketide synthase proteins is not present in this protein,
CC but lovB contains insteado a C-terminal condensation (C) domain that
CC has lost its condensation activity, but has gained a novel function
CC that is necessary for release of the final product (PubMed:23023987).
CC {ECO:0000269|PubMed:22733743, ECO:0000269|PubMed:23023987}.
CC -!- DOMAIN: Lacks an enoylreductase (ER) domain that reduces enoyl groups
CC to alkyl group which function is performed by the trans-acting enoyl
CC reductase lovC. {ECO:0000269|PubMed:22733743}.
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAU29410.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; CH476609; EAU29410.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_001209263.1; XM_001209263.1.
DR SMR; Q0C8M3; -.
DR STRING; 341663.Q0C8M3; -.
DR GeneID; 4319607; -.
DR eggNOG; KOG1202; Eukaryota.
DR OrthoDB; 5396558at2759; -.
DR UniPathway; UPA00875; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0050637; F:lovastatin nonaketide synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0140735; P:lovastatin biosynthetic process; ISS:GO_Central.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR CDD; cd02440; AdoMet_MTases; 1.
DR CDD; cd19532; C_PKS-NRPS; 1.
DR CDD; cd00833; PKS; 1.
DR Gene3D; 3.30.70.3290; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.30.559.10; Chloramphenicol acetyltransferase-like domain; 1.
DR Gene3D; 3.40.366.10; Malonyl-Coenzyme A Acyl Carrier Protein, domain 2; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 2.
DR Gene3D; 3.30.559.30; Nonribosomal peptide synthetase, condensation 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.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
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; IPR032821; PKS_assoc.
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; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR PANTHER; PTHR43775; FATTY ACID SYNTHASE; 1.
DR PANTHER; PTHR43775:SF20; HYBRID PKS-NRPS SYNTHETASE APDA; 1.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 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; SM00822; PKS_KR; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; ACP-like; 1.
DR SUPFAM; SSF52777; CoA-dependent acyltransferases; 2.
DR SUPFAM; SSF52151; FabD/lysophospholipase-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; PS52019; PKS_MFAS_DH; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..3038
FT /note="Lovastatin nonaketide synthase, polyketide synthase
FT component"
FT /id="PRO_0000283708"
FT DOMAIN 8..447
FT /note="Ketosynthase family 3 (KS3)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348,
FT ECO:0000305|PubMed:22733743"
FT DOMAIN 953..1267
FT /note="PKS/mFAS DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT DOMAIN 2463..2538
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:22733743"
FT REGION 562..889
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22733743"
FT REGION 953..1263
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22733743"
FT REGION 953..1089
FT /note="N-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1107..1267
FT /note="C-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1443..1543
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22733743"
FT REGION 2139..2437
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22733743"
FT REGION 2546..2602
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2602..2952
FT /note="Inactive Condensation domain"
FT /evidence="ECO:0000269|PubMed:23023987"
FT ACT_SITE 181
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 320
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 367
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 656
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 985
FT /note="Proton acceptor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT ACT_SITE 1174
FT /note="Proton donor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT MOD_RES 2498
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3038 AA; 335023 MW; DCBFC09FCC1C0094 CRC64;
MAQSMYPNEP IVVVGSGCRF PGDANTPSKL WELLQHPRDV QSRIPKERFD VDTFYHPDGK
HHGRTNAPYA YVLQDDLGAF DAAFFNIQAG EAESMDPQHR LLLETVYEAV TNAGMRIQDL
QGTSTAVYVG VMTHDYETVS TRDLENIPTY SATGVAVSVA SNRISYFFDW HGPSMTIDTA
CSSSLVAVHL AVQQLRTGQS SMAIAAGANL ILGPMTFVLE SKLSMLSPSG RSRMWDAGAD
GYARGEAVCS VVLKTLSQAL RDGDTIECVI RETGVNQDGR TTGITMPNHS AQEALIKATY
AQAGLDITKA EDRCQFFEAH GTGTPAGDPQ EAEAIATAFF GHEQVARSDG NERAPLFVGS
AKTVVGHTEG TAGLAGLMKA SFAVRHGVIP PNLLFDKISP RVAPFYKNLR IPTEATQWPA
LPPGQPRRAS VNSFGFGGTN AHAIIEEYME PEQNQLRVSN NEDCPPMTGV LSLPLVLSAK
SQRSLKIMME EMLQFLETHP EIHLHDLTWS LLRKRSVLPF RRAIVGHSHE TIRRALEDAI
EDGIVSSDFT TEVRGQPSVL GIFTGQGAQW PGMLKNLIEA SPYVRSIVRE LDDSLQSLPE
KYRPSWTLLD QFMLEGEASN VQYASFSQPL CCAVQIVLVR LLEAARIRFT AVVGHSSGEI
ACAFAAGLIS ASVAIRIAYL RGVVSAGGAR GTPGAMLAAG MSFEEAQEIC ELDAFEGRIC
VAASNSPDSV TFSGDANAID HLKSMLEDES TFARLLRVDT AYHSHHMLPC ADPYMQALEE
CGCAVADAGS PAGSVPWYSS VNAENRQMAA RDVTAEYWKD NLVSPVLFSH AVQRAVVTHK
ALDIGIEVGC HPALKSPCVA TIKDVLSGVD LAYTGCLERG KNDLDTFSRA LAYLWERFGA
SSFDADEFMR AVAPDRPCMS VSKLLPAYPW DHSRRYWVES RATRHHLRGP KPHLLLGKLS
EYSTPLSFQW LNFVRPRDIE WLDGHALQGQ TVFPAAGYIV MAMEAALMIA GTHAKQVQLL
EILDMSIDKA VIFDDEDSLV ELNLTADVSR NAGEAGSMTI SFKIDSCLSK EGNLSLSAKG
QLALMIGDVN SRTTSASDQH HLPPPEEEHP HMNRVNIKAF YHELGLMGYN YSKDFRRLHN
MQRADLRASG TIDFIPLMDE GNGCPLLLHP ASLDVAFQTV IGAYSSPGDR RLRCLYVPTH
VDRITLVPSL CLATAESGCE KVAFNTINTY DKGDYLSGDI AVFDAEQTTL FQVENITFKP
FSPPDASTDH AMFARWSWGP LTPDSLLDNP EYWATAQDKE AIPIIERIVY FYIRSFLNQL
TLEERQKAAF HLQKQIEWLE QVLASAKEGR HLWYDPGWEN DTEAQIEHLC TANSYHPHVR
LVQRVGQHLL PTVRSNGNPF DLLDHDGLLT EFYTNTLSFG PALHYARELV AQIAHRYQSM
DILEIGAGTG GATKYVLATP QLGFNSYTYT DISTGFFEQA REQFAPFEDR MVFEPLDIRR
SPAEQGFETH AYDLIIASNV LHATPDLEKT MAHARSLLKP GGQMVILEIT HKEHTRLGFI
FGLFADWWAG VDDGRCTEPF VSFDRWDAIL KRVGFSGVDS RTTDRDANLF PTSVFSTHAI
DATVEYLDAP LASSGTVKDS YPPLVVVGGQ TPKSQRLLND IKAIMPPRPL QTYKRLVDLL
DAEELPMKST FVMLTELDEE LFAGLTEETF EATKLLLTYS SNTVWLTENA WVQHPHQAST
IGMLRSIRRE HPDLGVHVLD VDAVETFDAT FLVEQVLRLE EHTDELASST TWTQEPEVSW
CKGRPWIPRL KRDLARNNRM NSSRRPIYEM IDSSRAPVAL QTAPDSSSYF LESAETWFVP
ESVRQMETKT VYVHFSCPHA LRVGQLGFFY LVQGHVQEGN REVPVVALAE RNASIVHVRP
DYIYTEADNN LSEGGGSLIV TVLAAAVLAE TVISTAKSLG VTDSILVLNP PSICGQMLLH
AGEEIGLQVH LATTSGNRSS VSAGDAKSWL TLHARDTDWH LRRVLPRGVQ AFVDLSADQS
CECLTQRMMK VLMPGCAHYR AADLFTDTVS TELHRGLRHQ ASLPAAYWEH VVSLARQGLS
SVSEGWEVMP CTQFAAHADK TRPDLSTVIS WPRESDKATL PTRVRSIDAE TLFAADKTYL
LVGLTGDLGR SLGRWMVQHG ACHIVLTSRN PQVNPKWLAH VEELGGRVTV LSMDVTSENS
VDAGLAKIKD LHLPPVGGIA FGPLVLQDVM LKNMELPMME MVLNPKVEGV RILHEKFSDP
TSSNPLDFFV MFSSIVAVMG NPGQANYSAA NCYLQALAQQ RVASGLAAST IDIGAVYGVG
FVTRAELEED FNAIRFMFDS VEEHELHTLF AEAVVAGRRA VHQQEQQRKF ATVLDMADLE
LTTGIPPLDP ALKDRITFFD DPRIGNLKIP EYRGAKAGEG AAGSKGSVKE QLLQATNLDQ
VRQIVIDGLS AKLQVTLQIP DGESVHPTIS LIDQGVDSLG AVTVGTWFSK QLYLDLPLLK
VLGGASIADL ADEAAARLPP SSIPLVAATD GGAESTDNTS ENEVSGREDT DLSAAATITE
PSSADEDDTE PGDEDVPRSH HPLSLGQEYS WRIQQGAEDP TVFNNTIGMF MKGPIDLKRL
YKALRAVLRR HEIFRTGFAN VDENGMAQLV FGQTKNKVQT IQVSDRAGAE EGYRQLVQTR
YNPAAGDTLR LVDFFWGQDD HLLVVAYHRL VGDGSTTENI FVEAGQLYDG RSLSPRVPQF
ADLAARQRAM LEDGRMEEDL AYWKEMHQRP SSIPVLPLMR PLVGNSSTSN TPNFQHCGSW
QQHEAVARLD PMVAFRIKER SRKHKATPMQ FYLAAYQVLL ARLTDSTDLT VGLADTNRAT
VDEMAAMGFF ANLLPLRFRD FRPHITFGEH LIATRDLVRE ALQHARVPYG VLLDQLGLEV
PVPTSNQPAP LLQAVFDYKQ GQAESGTIGG AKITEVIATR ERTPYDVVLE MSDDPTKDPL
LTAKLQSSRY EAHHPQAFLE SYMSLLSMFS MNPALKLA
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