PPSE_MYCBO
ID PPSE_MYCBO Reviewed; 1488 AA.
AC Q7TXL6; A0A1R3Y2M9; X2BLX7;
DT 05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Phenolphthiocerol/phthiocerol polyketide synthase subunit E {ECO:0000305};
DE EC=2.3.1.292 {ECO:0000250|UniProtKB:P9WQE1};
DE AltName: Full=(Phenol)carboxyphthiodiolenone synthase subunit E;
DE AltName: Full=Beta-ketoacyl-acyl-carrier-protein synthase I;
DE AltName: Full=Phthiocerol synthesis polyketide synthase type I PpsE;
GN Name=ppsE; OrderedLocusNames=BQ2027_MB2960;
OS Mycobacterium bovis (strain ATCC BAA-935 / AF2122/97).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=233413;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-935 / AF2122/97;
RX PubMed=12788972; DOI=10.1073/pnas.1130426100;
RA Garnier T., Eiglmeier K., Camus J.-C., Medina N., Mansoor H., Pryor M.,
RA Duthoy S., Grondin S., Lacroix C., Monsempe C., Simon S., Harris B.,
RA Atkin R., Doggett J., Mayes R., Keating L., Wheeler P.R., Parkhill J.,
RA Barrell B.G., Cole S.T., Gordon S.V., Hewinson R.G.;
RT "The complete genome sequence of Mycobacterium bovis.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:7877-7882(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=ATCC BAA-935 / AF2122/97;
RX PubMed=28385856; DOI=10.1128/genomea.00157-17;
RA Malone K.M., Farrell D., Stuber T.P., Schubert O.T., Aebersold R.,
RA Robbe-Austerman S., Gordon S.V.;
RT "Updated reference genome sequence and annotation of Mycobacterium bovis
RT AF2122/97.";
RL Genome Announc. 5:E00157-E00157(2017).
RN [3]
RP FUNCTION IN THE PHTHIOCEROL AND PHENOLPHTHIOCEROL BIOSYNTHESIS, PATHWAY,
RP AND DISRUPTION PHENOTYPE.
RC STRAIN=BCG;
RX PubMed=9201977; DOI=10.1074/jbc.272.27.16741;
RA Azad A.K., Sirakova T.D., Fernandes N.D., Kolattukudy P.E.;
RT "Gene knockout reveals a novel gene cluster for the synthesis of a class of
RT cell wall lipids unique to pathogenic mycobacteria.";
RL J. Biol. Chem. 272:16741-16745(1997).
RN [4]
RP PATHWAY, AND DISRUPTION PHENOTYPE.
RX PubMed=19197369; DOI=10.1371/journal.ppat.1000289;
RA Astarie-Dequeker C., Le Guyader L., Malaga W., Seaphanh F.K., Chalut C.,
RA Lopez A., Guilhot C.;
RT "Phthiocerol dimycocerosates of M. tuberculosis participate in macrophage
RT invasion by inducing changes in the organization of plasma membrane
RT lipids.";
RL PLoS Pathog. 5:E1000289-E1000289(2009).
CC -!- FUNCTION: Part of the PpsABCDE complex involved in the biosynthesis of
CC the lipid core common to phthiocerols and phenolphthiocerols by
CC successive additions of malonyl-CoA or methylmalonyl-CoA extender units
CC (PubMed:9201977). PpsA can accept as substrate the activated forms of
CC either icosanoyl (C20), docosanoyl (C22) or lignoceroyl (C24) groups
CC from FadD26, or a (4-hydroxyphenyl)-C17 or (4-hydroxyphenyl)-C19 fatty
CC acyl from FadD29 (By similarity). PpsA initiates the biosynthesis and
CC extends its substrate using a malonyl-CoA extender unit. The PpsB and
CC PpsC proteins add the second and third malonyl-CoA extender units. PpsD
CC adds an (R)-methylmalonyl unit and PpsE adds a second (R)-methylmalonyl
CC unit. The incorporation of the methylmalonyl units results in formation
CC of two branched methyl groups in the elongated product (By similarity).
CC {ECO:0000250|UniProtKB:P9WQE1, ECO:0000269|PubMed:9201977}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 (S)-methylmalonyl-CoA + 10 H(+) + icosanoyl-
CC [(phenol)carboxyphthiodiolenone synthase] + 3 malonyl-CoA + 5 NADPH =
CC C32-carboxyphthiodiolenone-[(phenol)carboxyphthiodiolenone synthase]
CC + 5 CO2 + 5 CoA + 2 H2O + 5 NADP(+); Xref=Rhea:RHEA:57748, Rhea:RHEA-
CC COMP:14985, Rhea:RHEA-COMP:14986, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57327, ChEBI:CHEBI:57384, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:87848, ChEBI:CHEBI:142236;
CC EC=2.3.1.292; Evidence={ECO:0000250|UniProtKB:P9WQE1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 (S)-methylmalonyl-CoA + docosanoyl-
CC [(phenol)carboxyphthiodiolenone synthase] + 10 H(+) + 3 malonyl-CoA +
CC 5 NADPH = C34-carboxyphthiodiolenone-[(phenol)carboxyphthiodiolenone
CC synthase] + 5 CO2 + 5 CoA + 2 H2O + 5 NADP(+); Xref=Rhea:RHEA:57752,
CC Rhea:RHEA-COMP:14987, Rhea:RHEA-COMP:14988, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57327, ChEBI:CHEBI:57384, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:142237, ChEBI:CHEBI:142238;
CC EC=2.3.1.292; Evidence={ECO:0000250|UniProtKB:P9WQE1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 (S)-methylmalonyl-CoA + 17-(4-hydroxyphenyl)heptadecanoyl-
CC [(phenol)carboxyphthiodiolenone synthase] + 10 H(+) + 3 malonyl-CoA +
CC 5 NADPH = C35-(phenol)carboxyphthiodiolenone-
CC [(phenol)carboxyphthiodiolenone synthase] + 5 CO2 + 5 CoA + 2 H2O + 5
CC NADP(+); Xref=Rhea:RHEA:57756, Rhea:RHEA-COMP:14272, Rhea:RHEA-
CC COMP:14989, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57327, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:133300,
CC ChEBI:CHEBI:142259; EC=2.3.1.292;
CC Evidence={ECO:0000250|UniProtKB:P9WQE1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 (S)-methylmalonyl-CoA + 19-(4-hydroxyphenyl)nonadecanoyl-
CC [(phenol)carboxyphthiodiolenone synthase] + 10 H(+) + 3 malonyl-CoA +
CC 5 NADPH = C37-(phenol)carboxyphthiodiolenone-
CC [(phenol)carboxyphthiodiolenone synthase] + 5 CO2 + 5 CoA + 2 H2O + 5
CC NADP(+); Xref=Rhea:RHEA:57760, Rhea:RHEA-COMP:14273, Rhea:RHEA-
CC COMP:14990, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57327, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:133301,
CC ChEBI:CHEBI:142260; EC=2.3.1.292;
CC Evidence={ECO:0000250|UniProtKB:P9WQE1};
CC -!- COFACTOR:
CC Name=NADP(+); Xref=ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P9WQE1};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000250};
CC Note=Binds 1 phosphopantetheine covalently. {ECO:0000250};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000269|PubMed:19197369, ECO:0000269|PubMed:9201977}.
CC -!- DISRUPTION PHENOTYPE: Disruption of the pps gene cluster abolishes the
CC production of both phthiocerol and phenolphthiocerol derivatives
CC (PubMed:9201977). Deletion of the gene abolishes the synthesis of
CC phthiocerol dimycocerosates (DIM) (PubMed:19197369).
CC {ECO:0000269|PubMed:19197369, ECO:0000269|PubMed:9201977}.
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DR EMBL; LT708304; SIU01581.1; -; Genomic_DNA.
DR RefSeq; NP_856605.1; NC_002945.3.
DR RefSeq; WP_003904964.1; NC_002945.4.
DR AlphaFoldDB; Q7TXL6; -.
DR SMR; Q7TXL6; -.
DR EnsemblBacteria; SIU01581; SIU01581; BQ2027_MB2960.
DR PATRIC; fig|233413.5.peg.3248; -.
DR OMA; WSQRCAG; -.
DR BioCyc; MetaCyc:MON-19630; -.
DR UniPathway; UPA00094; -.
DR Proteomes; UP000001419; Chromosome.
DR GO; GO:0034081; C:polyketide synthase complex; IMP:UniProtKB.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0071766; P:Actinobacterium-type cell wall biogenesis; IMP:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0008610; P:lipid biosynthetic process; IMP:UniProtKB.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 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; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR016039; Thiolase-like.
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; PF00550; PP-binding; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Fatty acid metabolism; Lipid metabolism; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..1488
FT /note="Phenolphthiocerol/phthiocerol polyketide synthase
FT subunit E"
FT /id="PRO_0000406951"
FT DOMAIN 930..1004
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 6..389
FT /note="Beta-ketoacyl synthase"
FT /evidence="ECO:0000250"
FT REGION 551..868
FT /note="Acyltransferase"
FT /evidence="ECO:0000250"
FT ACT_SITE 184
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 641
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT BINDING 1286..1331
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT MOD_RES 965
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1488 AA; 158746 MW; 14EC40432DB7F502 CRC64;
MSIPENAIAV VGMAGRFPGA KDVSAFWSNL RRGKESIVTL SEQELRDAGV SDKTLADPAY
VRRAPLLDGI DEFDAGFFGF PPLAAQVLDP QHRLFLQCAW HALEDAGADP ARFDGSIGVY
GTSSPSGYLL HNLLSHRDPN AVLAEGLNFD QFSLFLQNDK DFLATRISHA FNLRGPSIAV
QTACSSSLVA VHLACLSLLS GECDMALAGG SSLCIPHRVG YFTSPGSMVS AVGHCRPFDV
RADGTVFGSG VGLVVLKPLA AAIDAGDRIH AVIRGSAINN DGSAKMGYAA PNPAAQADVI
AEAHAVSGID SSTVSYVECH GTGTPLGDPI EIQGLRAAFE VSQTSRSAPC VLGSVKSNIG
HLEVAAGIAG LIKTILCLKN KALPATLHYT SPNPELRLDQ SPFVVQSKYG PWECDGVRRA
GVSSFGVGGT NAHVVLEEAP AEASEVSAHA EPAGPQVILL SAQTAAALGE SRTALAAALE
TQDGPRLSDV AYTLARRRKH NVTMAAVVHD REHAATVLRA AEHDNVFVGE AAHDGEHGDR
ADAAPTSDRV VFLFPGQGAQ HVGMAKGLYD TEPVFAQHFD TCAAGFRDET GIDLHAEVFD
GTATDLERID RSQPALFTVE YALAKLVDTF GVRAGAYIGY STGEYIAATL AGVFDLQTAI
KTVSLRARLM HESPPGAMVA VALGPDDVTQ YLPPEVELSA VNDPGNCVVA GPKDQIRALR
QRLTEAGIPV RRVRATHAFH TSAMDPMLGQ FQEFLSRQQL RPPRTPLLSN LTGSWMSDQQ
VVDPASWTRQ ISSPIRFADE LDVVLAAPSR ILVEVGPGGS LTGSAMRHPK WSTTHRTVRL
MRHPLQDVDD RDTFLRALGE LWSAGVEVDW TPRRPAVPHL VSLPGYPFAR QRHWVEPNHT
VWAQAPGANN GSPAGTADGS TAATVDAARN GESQTEVTLQ RIWSQCLGVS SVDRNANFFD
LGGDSLMAIS IAMAAANEGL TITPQDLYEY PTLASLTAAV DASFASSGLA KPPEAQANPA
VPPNVTYFLD RGLRDTGRCR VPLILRLDPK IGLPDIRAVL TAVVNHHDAL RLHLVGNDGI
WEQHIAAPAE FTGLSNRSVP DGVAAGSPEE RAAVLGILAE LLEDQTDPNA PLAAVHIAAA
HGGPHYLCLA IHAMVTDDSS RQILATDIVT AFGQRLAGEE ITLEPVSTGW REWSLRCAAL
ATHPAALDTR SYWIENSTKA TLWLADALPN AHTAHPPRAD ELTKLSSTLS VEQTSELDDG
RRRFRRSIQT ILLAALGRTI AQTVGEGVVA VELEGEGRSV LRPDVDLRRT VGWFTTYYPV
PLACATGLGA LAQLDAVHNT LKSVPHYGIG YGLLRYVYAP TGRVLGAQRT PDIHFRYAGV
IPELPSGDAP VQFDSDMTLP VREPIPGMGH AIELRVYRFG GSLHLDWWYD TRRIPAATAE
ALERTFPLAL SALIQEAIAA EHTEHDDSEI VGEPEAGALV DLSSMDAG
