PPSC_MYCBO
ID PPSC_MYCBO Reviewed; 2188 AA.
AC Q7TXL8; A0A1R3Y2L7; X2BMJ1;
DT 05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Phenolphthiocerol/phthiocerol polyketide synthase subunit C {ECO:0000305};
DE EC=2.3.1.292 {ECO:0000250|UniProtKB:P96202};
DE AltName: Full=(Phenol)carboxyphthiodiolenone synthase subunit C;
DE AltName: Full=Beta-ketoacyl-acyl-carrier-protein synthase I;
DE AltName: Full=Phthiocerol synthesis polyketide synthase type I PpsC;
GN Name=ppsC; OrderedLocusNames=BQ2027_MB2958;
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).
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:P96202, 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:P96202};
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:P96202};
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:P96202};
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:P96202};
CC -!- COFACTOR:
CC Name=NADP(+); Xref=ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P96202};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000250|UniProtKB:P96202};
CC Note=Binds 1 phosphopantetheine covalently.
CC {ECO:0000250|UniProtKB:P96202};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000269|PubMed:9201977}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Disruption of the pps gene cluster abolishes the
CC production of both phthiocerol and phenolphthiocerol derivatives.
CC {ECO:0000269|PubMed:9201977}.
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DR EMBL; LT708304; SIU01579.1; -; Genomic_DNA.
DR RefSeq; NP_856603.1; NC_002945.3.
DR RefSeq; WP_003414837.1; NC_002945.4.
DR AlphaFoldDB; Q7TXL8; -.
DR SMR; Q7TXL8; -.
DR PRIDE; Q7TXL8; -.
DR EnsemblBacteria; SIU01579; SIU01579; BQ2027_MB2958.
DR PATRIC; fig|233413.5.peg.3246; -.
DR OMA; KMRGGEF; -.
DR BioCyc; MetaCyc:MON-19628; -.
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:0097041; P:phenolic phthiocerol biosynthetic process; IMP:UniProtKB.
DR GO; GO:0097040; P:phthiocerol biosynthetic process; IMP: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; IPR013154; ADH_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; 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; IPR020843; PKS_ER.
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; PF08240; ADH_N; 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; SM00829; PKS_ER; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 3.
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; Transferase.
FT CHAIN 1..2188
FT /note="Phenolphthiocerol/phthiocerol polyketide synthase
FT subunit C"
FT /id="PRO_0000406947"
FT DOMAIN 2069..2145
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 37..465
FT /note="Beta-ketoacyl synthase"
FT /evidence="ECO:0000250"
FT REGION 572..890
FT /note="Acyltransferase"
FT /evidence="ECO:0000250"
FT REGION 928..1093
FT /note="Dehydratase"
FT /evidence="ECO:0000250"
FT REGION 1467..1778
FT /note="Enoylreductase"
FT /evidence="ECO:0000250"
FT REGION 1802..1981
FT /note="Beta-ketoacyl reductase"
FT /evidence="ECO:0000250"
FT ACT_SITE 210
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 660
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT BINDING 1803..1848
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT MOD_RES 2105
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2188 AA; 230622 MW; 3C431C011F01F1A2 CRC64;
MTAATPDRRA IITEALHKID DLTARLEIAE KSSSEPIAVI GMGCRFPGGV NNPEQFWDLL
CAGRSGIVRV PAQRWDADAY YCDDHTVPGT ICSTEGGFLT SWQPDEFDAE FFSISPREAA
AMDPQQRLLI EVAWEALEDA GVPQHTIRGT QTSVFVGVTA YDYMLTLAGR LRPVDLDAYI
PTGNSANFAA GRLAYILGAR GPAVVIDTAC SSSLVAVHLA CQSLRGRESD MALVGGTNLL
LSPGPSIACS RWGMLSPEGR CKTFDASADG YVRGEGAAVV VLKRLDDAVR DGNRILAVVR
GSAVNQDGAS SGVTVPNGPA QQALLAKALT SSKLTAADID YVEAHGTGTP LGDPIELDSL
SKVFSDRAGS DQLVIGSVKT NLGHLEAAAG VAGLMKAVLA VHNGYIPRHL NFHQLTPHAS
EAASRLRIAA DGIDWPTTGR PRRAGVSSFG VSGTNAHVVI EQAPDPMAAA GTEPQRGPVP
AVSTLVVFGK TAPRVAATAS VLADWLDGPG AAVPLADVAH TLNHHRARQT RFGTVAAVDR
RQAVIGLRAL AAGQSAPGVV APREGSIGGG TVFVYSGRGS QWAGMGRQLL ADEPAFAAAI
AELEPEFVAQ GGFSLRDVIA GGKELVGIEQ IQLGLIGMQL ALTALWRSYG VTPDAVIGHS
MGEVAAAVVA GALTPAQGLR VTAVRSRLMA PLSGQGTMAL LELDAEATEA LIADYPEVSL
GIYASPRQTV ISGPPLLIDE LIDKVRQQNG FATRVNIEVA PHNPAMDALQ PAMRSELADL
TPQPPTIPII STTYADLGIS LGSGPRFDAE HWATNMRNPV RFHQAIAHAG ADHHTFIEIS
AHPLLTHSIS DTLRASYDVD NYLSIGTLQR DAHDTLEFHT NLNTTHTTHP PQTPHPPEPH
PVLPTTPWQH TQHWITATSA AYHRPDTHPL LGVGVTDPTN GTRVWESELD PDLLWLADHV
IDDLVVLPGA AYAEIALAAA TDTFAVEQDQ PWMISELDLR QMLHVTPGTV LVTTLTGDEQ
RCQVEIRTRS GSSGWTTHAT ATVARAEPLA PLDHEGQRRE VTTADLEDQL DPDDLYQRLR
GAGQQHGPAF QGIVGLAVTQ AGVARAQVRL PASARTGSRE FMLHPVMMDI ALQTLGATRT
ATDLAGGQDA RQGPSSNSAL VVPVRFAGVH VYGDITRGVR AVGSLAAAGD RLVGEVVLTD
ANGQPLLVVD EVEMAVLGSG SGATELTNRL FMLEWEPAPL EKTAEATGAL LLIGDPAAGD
PLLPALQSSL RDRITDLELA SAADEATLRA AISRTSWDGI VVVCPPRAND ESMPDEAQLE
LARTRTLLVA SVVETVTRMG ARKSPRLWIV TRGAAQFDAG ESVTLAQTGL RGIARVLTFE
HSELNTTLVD IEPDGTGSLA ALAEELLAGS EADEVALRDG QRYVNRLVPA PTTTSGDLAA
EARHQVVNLD SSGASRAAVR LQIDQPGRLD ALNVHEVKRG RPQGDQVEVR VVAAGLNFSD
VLKAMGVYPG LDGAAPVIGG ECVGYVTAIG DEVDGVEVGQ RVIAFGPGTF GTHLGTIADL
VVPIPDTLAD NEAATFGVAY LTAWHSLCEV GRLSPGERVL IHSATGGVGM AAVSIAKMIG
ARIYTTAGSD AKREMLSRLG VEYVGDSRSV DFADEILELT DGYGVDVVLN SLAGEAIQRG
VQILAPGGRF IELGKKDVYA DASLGLAALA KSASFSVVDL DLNLKLQPAR YRQLLQHILQ
HVADGKLEVL PVTAFSLHDA ADAFRLMASG KHTGKIVISI PQHGSIEAIA APPPLPLVSR
DGGYLIVGGM GGLGFVVARW LAEQGAGLIV LNGRSAPSDE VAAAIAELNA SGSRIEVITG
DITEPDTAER LVRAVEDAGF RLAGVVHSAM VLADEIVLNM TDSAARRVFA PKVTGSWRLH
VATAARDVDW WLTFSSAAAL LGTPGQGAYA AANSWVDGLV AHRRSAGLPA VGINWGPWAD
VGRAQFFKDL GVEMINAEQG LAAMQAVLTA DRGRTGVFSL DARQWFQSFP AVAGSSLFAK
LHDSAARKSG QRRGGGAIRA QLDALDAAER PGHLASAIAD EIRAVLRSGD PIDHHRPLET
LGLDSLMGLE LRNRLEASLG ITLPVALVWA YPTISDLATA LCERMDYATP AAAQEISDTE
PELSDEEMDL LADLVDASEL EAATRGES
