ID   PPSA_MYCBO              Reviewed;        1876 AA.
AC   Q7TXM0; A0A1R3Y2S1; X2BM73;
DT   05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2003, sequence version 1.
DT   03-AUG-2022, entry version 124.
DE   RecName: Full=Phenolphthiocerol/phthiocerol polyketide synthase subunit A {ECO:0000305};
DE            EC=2.3.1.292 {ECO:0000250|UniProtKB:P9WQE7};
DE   AltName: Full=(Phenol)carboxyphthiodiolenone synthase subunit A;
DE   AltName: Full=Beta-ketoacyl-acyl-carrier-protein synthase I;
DE   AltName: Full=Phthiocerol synthesis polyketide synthase type I PpsA;
GN   Name=ppsA; OrderedLocusNames=BQ2027_MB2956;
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:P9WQE7, 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:P9WQE7};
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:P9WQE7};
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:P9WQE7};
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:P9WQE7};
CC   -!- COFACTOR:
CC       Name=NADP(+); Xref=ChEBI:CHEBI:58349;
CC         Evidence={ECO:0000250|UniProtKB:P9WQE7};
CC   -!- COFACTOR:
CC       Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC         Evidence={ECO:0000250};
CC       Note=Binds 2 phosphopantetheines covalently. {ECO:0000250};
CC   -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC       {ECO:0000269|PubMed:9201977}.
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; SIU01577.1; -; Genomic_DNA.
DR   RefSeq; NP_856601.1; NC_002945.3.
DR   RefSeq; WP_010950800.1; NC_002945.4.
DR   AlphaFoldDB; Q7TXM0; -.
DR   SMR; Q7TXM0; -.
DR   EnsemblBacteria; SIU01577; SIU01577; BQ2027_MB2956.
DR   PATRIC; fig|233413.5.peg.3244; -.
DR   OMA; FFLEVSW; -.
DR   BioCyc; MetaCyc:MON-17242; -.
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; -; 2.
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; 2.
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; 2.
DR   SUPFAM; SSF47336; SSF47336; 2.
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; 2.
DR   PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE   1: Evidence at protein level;
KW   Fatty acid metabolism; Lipid metabolism; Multifunctional enzyme; NADP;
KW   Oxidoreductase; Phosphopantetheine; Phosphoprotein; Repeat; Transferase.
FT   CHAIN           1..1876
FT                   /note="Phenolphthiocerol/phthiocerol polyketide synthase
FT                   subunit A"
FT                   /id="PRO_0000406945"
FT   DOMAIN          9..83
FT                   /note="Carrier 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   DOMAIN          1759..1836
FT                   /note="Carrier 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          104..529
FT                   /note="Beta-ketoacyl synthase"
FT                   /evidence="ECO:0000250"
FT   REGION          624..950
FT                   /note="Acyltransferase"
FT                   /evidence="ECO:0000250"
FT   REGION          1104..1130
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1491..1728
FT                   /note="Beta-ketoacyl reductase"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        1104..1121
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        273
FT                   /note="For beta-ketoacyl synthase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT   ACT_SITE        720
FT                   /note="For malonyltransferase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT   BINDING         1492..1551
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         43
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   MOD_RES         1796
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   1876 AA;  198848 MW;  D44006C79AEF6AAE CRC64;
     MTGSISGEAD LRHWLIDYLV TNIGCTPDEV DPDLSLADLG VSSRDAVVLS GELSELLGRT
     VSPIDFWEHP TINALAAYLA APEPSPDSDA AVKRGARNSL DEPIAVVGMG CRFPGGISCP
     EALWDFLCER RSSISQVPPQ RWQPFEGGPP EVAAALARTT RWGSFLPDID AFDAEFFEIS
     PSEADKMDPQ QRLLLEVAWE ALEHAGIPPG TLRRSATGVF AGACLSEYGA MASADLSQVD
     GWSNSGGAMS IIANRLSYFL DLRGPSVAVD TACSSSLVAI HLACQSLRTQ DCHLAIAAGV
     NLLLSPAVFR GFDQVGALSP TGQCRAFDAT ADGFVRGEGA GVVVLKRLTD AQRDGDRVLA
     VICGSAVTQD GRSNGLMAPN PAAQMAVLRA AYTNAGMQPS EVDYVEAHGT GTLLGDPIEA
     RALGTVLGRG RPEDSPLLIG SVKTNLGHTE AAAGIAGFIK TVLAVQHGQI PPNQHFETAN
     PHIPFTDLRM KVVDTQTEWP ATGHPRRAGV SSFGFGGTNA HVVIEQGQEV RPAPGQGLSP
     AVSTLVVAGK TMQRVSATAG MLADWMEGPG ADVALADVAH TLNHHRSRQP KFGTVVARDR
     TQAIAGLRAL AAGQHAPGVV NPAEGSPGPG TVFVYSGRGS QWAGMGRQLL ADEPAFAAAV
     AELEPVFVEQ AGFSLHDVLA NGEELVGIEQ IQLGLIGMQL ALTELWCSYG VQPDLVIGHS
     MGEVAAAVVA GALTPAEGLR VTATRSRLMA PLSGQGGMAL LELDAPTTEA LIADFPQVTL
     GIYNSPRQTV IAGPTEQIDE LITRVRARDR FASRVNIEVA PHNPAMDALQ PAMRSELADL
     TPRTPTIGII STTYADLHTQ PVFDAEHWAT NMRNPVHFQQ AIASAGSGAD GAYHTFIEIS
     AHPLLTQAII DTLHSAQPGA RYTSLGTLQR DTDDVVTFRT NLNKAHTIHP PHTPHPPEPH
     PPIPTTPWQH TRHWITTKYP AGSVGSAPRA GTLLGQHTTV ATVSASPPSH LWQARLAPDA
     KPYQGGHRFH QVEVVPASVV LHTILSAATE LGYSALSEVR FEQPIFADRP RLIQVVADNR
     AISLASSPAA GTPSDRWTRH VTAQLSSSPS DSASSLNEHH RANGQPPERA HRDLIPDLAE
     LLAMRGIDGL PFSWTVASWT QHSSNLTVAI DLPEALPEGS TGPLLDAAVH LAALSDVADS
     RLYVPASIEQ ISLGDVVTGP RSSVTLNRTA HDDDGITVDV TVAAHGEVPS LSMRSLRYRA
     LDFGLDVGRA QPPASTGPVE AYCDATNFVH TIDWQPQTVP DATHPGAEQV THPGPVAIIG
     DDGAALCETL EGAGYQPAVM SDGVSQARYV VYVADSDPAG ADETDVDFAV RICTEITGLV
     RTLAERDADK PAALWILTRG VHESVAPSAL RQSFLWGLAG VIAAEHPELW GGLVDLAIND
     DLGEFGPALA ELLAKPSKSI LVRRDGVVLA PALAPVRGEP ARKSLQCRPD AAYLITGGLG
     ALGLLMADWL ADRGAHRLVL TGRTPLPPRR DWQLDTLDTE LRRRIDAIRA LEMRGVTVEA
     VAADVGCRED VQALLAARDR DGAAPIRGII HAAGITNDQL VTSMTGDAVR QVMWPKIGGS
     QVLHDAFPPG SVDFFYLTAS AAGIFGIPGQ GSYAAANSYL DALARARRQQ GCHTMSLDWV
     AWRGLGLAAD AQLVSEELAR MGSRDITPSE AFTAWEFVDG YDVAQAVVVP MPAPAGADGS
     GANAYLLPAR NWSVMAATEV RSELEQGLRR IIAAELRVPE KELDTDRPFA ELGLNSLMAM
     AIRREAEQFV GIELSATMLF NHPTVKSLAS YLAKRVAPHD VSQDNQISAL SSSAGSVLDS
     LFDRIESAPP EAERSV