PPSD_MYCTU
ID PPSD_MYCTU Reviewed; 1827 AA.
AC P9WQE3; L0TDZ9; P96203; Q7D6F0;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 47.
DE RecName: Full=Phenolphthiocerol/phthiocerol polyketide synthase subunit D {ECO:0000305};
DE EC=2.3.1.292 {ECO:0000269|PubMed:15749014, ECO:0000305|PubMed:20553505};
DE AltName: Full=(Phenol)carboxyphthiodiolenone synthase subunit D;
DE AltName: Full=Beta-ketoacyl-acyl-carrier-protein synthase I;
DE AltName: Full=Phthiocerol synthesis polyketide synthase type I PpsD;
GN Name=ppsD; OrderedLocusNames=Rv2934;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND PATHWAY.
RX PubMed=15749014; DOI=10.1016/j.molcel.2005.02.009;
RA Trivedi O.A., Arora P., Vats A., Ansari M.Z., Tickoo R., Sridharan V.,
RA Mohanty D., Gokhale R.S.;
RT "Dissecting the mechanism and assembly of a complex virulence mycobacterial
RT lipid.";
RL Mol. Cell 17:631-643(2005).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20553505; DOI=10.1111/j.1742-4658.2010.07688.x;
RA Simeone R., Leger M., Constant P., Malaga W., Marrakchi H., Daffe M.,
RA Guilhot C., Chalut C.;
RT "Delineation of the roles of FadD22, FadD26 and FadD29 in the biosynthesis
RT of phthiocerol dimycocerosates and related compounds in Mycobacterium
RT tuberculosis.";
RL FEBS J. 277:2715-2725(2010).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
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:15749014, PubMed:20553505). PpsA can accept as substrate the
CC activated forms of either icosanoyl (C20), docosanoyl (C22) or
CC lignoceroyl (C24) groups from FadD26, or a (4-hydroxyphenyl)-C17 or (4-
CC hydroxyphenyl)-C19 fatty acyl from FadD29 (PubMed:15749014,
CC PubMed:20553505). PpsA initiates the biosynthesis and extends its
CC substrate using a malonyl-CoA extender unit. The PpsB and PpsC proteins
CC add the second and third malonyl-CoA extender units. PpsD adds an (R)-
CC methylmalonyl unit and PpsE adds a second (R)-methylmalonyl unit. The
CC incorporation of the methylmalonyl units results in formation of two
CC branched methyl groups in the elongated product (PubMed:15749014).
CC {ECO:0000269|PubMed:15749014, ECO:0000269|PubMed:20553505}.
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:0000269|PubMed:15749014,
CC ECO:0000305|PubMed:20553505};
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:0000269|PubMed:15749014,
CC ECO:0000305|PubMed:20553505};
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:0000269|PubMed:15749014, ECO:0000305|PubMed:20553505};
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:0000269|PubMed:15749014, ECO:0000305|PubMed:20553505};
CC -!- COFACTOR:
CC Name=NADP(+); Xref=ChEBI:CHEBI:58349;
CC Evidence={ECO:0000269|PubMed:15749014};
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:15749014}.
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DR EMBL; AL123456; CCP45737.1; -; Genomic_DNA.
DR PIR; B70984; B70984.
DR RefSeq; NP_217450.1; NC_000962.3.
DR RefSeq; WP_003899549.1; NZ_NVQJ01000015.1.
DR AlphaFoldDB; P9WQE3; -.
DR SMR; P9WQE3; -.
DR STRING; 83332.Rv2934; -.
DR PaxDb; P9WQE3; -.
DR GeneID; 887172; -.
DR KEGG; mtu:Rv2934; -.
DR TubercuList; Rv2934; -.
DR eggNOG; COG1028; Bacteria.
DR eggNOG; COG3321; Bacteria.
DR OMA; CARTHAE; -.
DR PhylomeDB; P9WQE3; -.
DR UniPathway; UPA00094; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0034081; C:polyketide synthase complex; ISS:UniProtKB.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0004312; F:fatty acid synthase activity; IBA:GO_Central.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0071770; P:DIM/DIP cell wall layer assembly; IDA:MTBBASE.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IDA:MTBBASE.
DR GO; GO:0097041; P:phenolic phthiocerol biosynthetic process; ISS:UniProtKB.
DR GO; GO:0097040; P:phthiocerol biosynthetic process; ISS:UniProtKB.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 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; 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; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 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; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF51735; SSF51735; 2.
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.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Fatty acid metabolism; Lipid metabolism; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW Transferase.
FT CHAIN 1..1827
FT /note="Phenolphthiocerol/phthiocerol polyketide synthase
FT subunit D"
FT /id="PRO_0000406950"
FT DOMAIN 1706..1785
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 38..464
FT /note="Beta-ketoacyl synthase"
FT /evidence="ECO:0000250"
FT REGION 566..876
FT /note="Acyltransferase"
FT /evidence="ECO:0000250"
FT REGION 910..1076
FT /note="Dehydratase"
FT /evidence="ECO:0000250"
FT REGION 1439..1617
FT /note="Beta-ketoacyl reductase"
FT /evidence="ECO:0000250"
FT REGION 1807..1827
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 207
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 654
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT BINDING 1440..1485
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT MOD_RES 1745
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1827 AA; 193315 MW; 88A3C1392838D953 CRC64;
MTSLAERAAQ LSPNARAALA RELVRAGTTF PTDICEPVAV VGIGCRFPGN VTGPESFWQL
LADGVDTIEQ VPPDRWDADA FYDPDPSASG RMTTKWGGFV SDVDAFDADF FGITPREAVA
MDPQHRMLLE VAWEALEHAG IPPDSLSGTR TGVMMGLSSW DYTIVNIERR ADIDAYLSTG
TPHCAAVGRI AYLLGLRGPA VAVDTACSSS LVAIHLACQS LRLRETDVAL AGGVQLTLSP
FTAIALSKWS ALSPTGRCNS FDANADGFVR GEGCGVVVLK RLADAVRDQD RVLAVVRGSA
TNSDGRSNGM TAPNALAQRD VITSALKLAD VTPDSVNYVE THGTGTVLGD PIEFESLAAT
YGLGKGQGES PCALGSVKTN IGHLEAAAGV AGFIKAVLAV QRGHIPRNLH FTRWNPAIDA
SATRLFVPTE SAPWPAAAGP RRAAVSSFGL SGTNAHVVVE QAPDTAVAAA GGMPYVSALN
VSGKTAARVA SAAAVLADWM SGPGAAAPLA DVAHTLNRHR ARHAKFATVI ARDRAEAIAG
LRALAAGQPR VGVVDCDQHA GGPGRVFVYS GQGSQWASMG QQLLANEPAF AKAVAELDPI
FVDQVGFSLQ QTLIDGDEVV GIDRIQPVLV GMQLALTELW RSYGVIPDAV IGHSMGEVSA
AVVAGALTPE QGLRVITTRS RLMARLSGQG AMALLELDAD AAEALIAGYP QVTLAVHASP
RQTVIAGPPE QVDTVIAAVA TQNRLARRVE VDVASHHPII DPILPELRSA LADLTPQPPS
IPIISTTYES AQPVADADYW SANLRNPVRF HQAVTAAGVD HNTFIEISPH PVLTHALTDT
LDPDGSHTVM STMNRELDQT LYFHAQLAAV GVAASEHTTG RLVDLPPTPW HHQRFWVTDR
SAMSELAATH PLLGAHIEMP RNGDHVWQTD VGTEVCPWLA DHKVFGQPIM PAAGFAEIAL
AAASEALGTA ADAVAPNIVI NQFEVEQMLP LDGHTPLTTQ LIRGGDSQIR VEIYSRTRGG
EFCRHATAKV EQSPRECAHA HPEAQGPATG TTVSPADFYA LLRQTGQHHG PAFAALSRIV
RLADGSAETE ISIPDEAPRH PGYRLHPVVL DAALQSVGAA IPDGEIAGSA EASYLPVSFE
TIRVYRDIGR HVRCRAHLTN LDGGTGKMGR IVLINDAGHI AAEVDGIYLR RVERRAVPLP
LEQKIFDAEW TESPIAAVPA PEPAAETTRG SWLVLADATV DAPGKAQAKS MADDFVQQWR
SPMRRVHTAD IHDESAVLAA FAETAGDPEH PPVGVVVFVG GASSRLDDEL AAARDTVWSI
TTVVRAVVGT WHGRSPRLWL VTGGGLSVAD DEPGTPAAAS LKGLVRVLAF EHPDMRTTLV
DLDITQDPLT ALSAELRNAG SGSRHDDVIA WRGERRFVER LSRATIDVSK GHPVVRQGAS
YVVTGGLGGL GLVVARWLVD RGAGRVVLGG RSDPTDEQCN VLAELQTRAE IVVVRGDVAS
PGVAEKLIET ARQSGGQLRG VVHAAAVIED SLVFSMSRDN LERVWAPKAT GALRMHEATA
DCELDWWLGF SSAASLLGSP GQAAYACASA WLDALVGWRR ASGLPAAVIN WGPWSEVGVA
QALVGSVLDT ISVAEGIEAL DSLLAADRIR TGVARLRADR ALVAFPEIRS ISYFTQVVEE
LDSAGDLGDW GGPDALADLD PGEARRAVTE RMCARIAAVM GYTDQSTVEP AVPLDKPLTE
LGLDSLMAVR IRNGARADFG VEPPVALILQ GASLHDLTAD LMRQLGLNDP DPALNNADTI
RDRARQRAAA RHGAAMRRRP KPEVQGG
