ID   PHAS_MYCTA              Reviewed;        2126 AA.
AC   A5U9F4;
DT   08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT   10-JUL-2007, sequence version 1.
DT   03-AUG-2022, entry version 89.
DE   RecName: Full=Phthioceranic/hydroxyphthioceranic acid synthase {ECO:0000250|UniProtKB:P9WQE9};
DE            EC=2.3.1.287 {ECO:0000250|UniProtKB:P9WQE9};
DE   AltName: Full=Polyketide synthase pks2 {ECO:0000250|UniProtKB:P9WQE9};
GN   Name=pks2; OrderedLocusNames=MRA_3865;
OS   Mycobacterium tuberculosis (strain ATCC 25177 / H37Ra).
OC   Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC   Mycobacterium; Mycobacterium tuberculosis complex.
OX   NCBI_TaxID=419947;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 25177 / H37Ra;
RX   PubMed=18584054; DOI=10.1371/journal.pone.0002375;
RA   Zheng H., Lu L., Wang B., Pu S., Zhang X., Zhu G., Shi W., Zhang L.,
RA   Wang H., Wang S., Zhao G., Zhang Y.;
RT   "Genetic basis of virulence attenuation revealed by comparative genomic
RT   analysis of Mycobacterium tuberculosis strain H37Ra versus H37Rv.";
RL   PLoS ONE 3:E2375-E2375(2008).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=7 (S)-methylmalonyl-CoA + 21 H(+) + hexadecanoyl-
CC         [(hydroxy)phthioceranic acid synthase] + 14 NADPH = C37-
CC         phthioceranyl-[(hydroxy)phthioceranic acid synthase] + 7 CO2 + 7 CoA
CC         + 7 H2O + 14 NADP(+); Xref=Rhea:RHEA:58908, Rhea:RHEA-COMP:15244,
CC         Rhea:RHEA-COMP:15246, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57327,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:78483,
CC         ChEBI:CHEBI:142473; EC=2.3.1.287;
CC         Evidence={ECO:0000250|UniProtKB:P9WQE9};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=8 (S)-methylmalonyl-CoA + 24 H(+) + hexadecanoyl-
CC         [(hydroxy)phthioceranic acid synthase] + 16 NADPH = C40-
CC         phthioceranyl-[(hydroxy)phthioceranic acid synthase] + 8 CO2 + 8 CoA
CC         + 8 H2O + 16 NADP(+); Xref=Rhea:RHEA:58904, Rhea:RHEA-COMP:15244,
CC         Rhea:RHEA-COMP:15245, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57327,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:78483,
CC         ChEBI:CHEBI:142472; EC=2.3.1.287;
CC         Evidence={ECO:0000250|UniProtKB:P9WQE9};
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   -!- MISCELLANEOUS: In strain H37Ra, the sulfolipid-1 (SL-1) is not
CC       synthesized.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; CP000611; ABQ75654.1; -; Genomic_DNA.
DR   RefSeq; WP_003900763.1; NZ_CP016972.1.
DR   AlphaFoldDB; A5U9F4; -.
DR   SMR; A5U9F4; -.
DR   STRING; 419947.MRA_3865; -.
DR   EnsemblBacteria; ABQ75654; ABQ75654; MRA_3865.
DR   KEGG; mra:MRA_3865; -.
DR   eggNOG; COG0604; Bacteria.
DR   eggNOG; COG1028; Bacteria.
DR   eggNOG; COG3321; Bacteria.
DR   HOGENOM; CLU_000022_35_5_11; -.
DR   OMA; KDVQHYT; -.
DR   OrthoDB; 1123553at2; -.
DR   Proteomes; UP000001988; Chromosome.
DR   GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:InterPro.
DR   GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR   GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
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; IPR013149; ADH-like_C.
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; PF00107; ADH_zinc_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   3: Inferred from homology;
KW   Acyltransferase; Fatty acid biosynthesis; Fatty acid metabolism;
KW   Lipid biosynthesis; Lipid metabolism; Multifunctional enzyme; NADP;
KW   Phosphopantetheine; Phosphoprotein; Transferase.
FT   CHAIN           1..2126
FT                   /note="Phthioceranic/hydroxyphthioceranic acid synthase"
FT                   /id="PRO_0000329011"
FT   DOMAIN          2040..2126
FT                   /note="Carrier"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          1..449
FT                   /note="Beta-ketoacyl synthase (KS)"
FT                   /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT   REGION          449..549
FT                   /note="Linker domain (LD)"
FT                   /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT   REGION          550..849
FT                   /note="Acyltransferase (AT)"
FT                   /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT   REGION          909..1191
FT                   /note="Dehydratase (DH)"
FT                   /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT   REGION          1227..1398
FT                   /note="Pseudo beta-ketoacyl reductase (PsiKR)"
FT                   /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT   REGION          1426..1750
FT                   /note="Enoylreductase (ER)"
FT                   /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT   REGION          1772..2019
FT                   /note="Beta-ketoacyl reductase (KR)"
FT                   /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT   ACT_SITE        196
FT                   /note="Acyl-thioester intermediate; for beta-ketoacyl
FT                   synthase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT   ACT_SITE        641
FT                   /note="Acyl-ester intermediate; for acyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:A0R1E8"
FT   ACT_SITE        947
FT                   /note="Proton acceptor; for dehydratase activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q03132"
FT   ACT_SITE        1115
FT                   /note="Proton donor; for dehydratase activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q03132"
FT   BINDING         1780..1783
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q03131"
FT   BINDING         1803..1806
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q03131"
FT   BINDING         1831..1832
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q03131"
FT   BINDING         1904..1905
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q03131"
FT   MOD_RES         2075
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   2126 AA;  225776 MW;  224469098DE741C6 CRC64;
     MGLGSAASGT GADRGAWTLA EPRVTPVAVI GMACRLPGGI DSPELLWKAL LRGDDLITEV
     PPDRWDCDEF YDPQPGVPGR TVCKWGGFLD NPADFDCEFF GIGEREAIAI DPQQRLLLET
     SWEAMEHAGL TQQTLAGSAT GVFAGVTHGD YTMVAADAKQ LEEPYGYLGN SFSMASGRVA
     YAMRLHGPAI TVDTACSSGL TAVHMACRSL HEGESDVALA GGVALMLEPR KAAAGSALGM
     LSPTGRCRAF DVAADGFVSG EGCAVVVLKR LPDALADGDR ILAVIRGTSA NQDGHTVNIA
     TPSQPAQVAA YRAALAAGGV DAATVGMVEA HGPGTPIGDP IEYASVSEVY GVDGPCALAS
     VKTNFGHTQS TAGVLGLIKV VLALKHGVVP RNLHFTRLPD EIAGITTNLF VPEVTTPWPT
     NGRQVPRRAA VSSYGFSGTN VHAVVEQAPQ TEAQPHAAST PPTGTPALFT LSASSADALR
     QTAQRLTDWI QQHADSLVLS DLAYTLARRR THRSVRTAVI ASSVDELIAG LGEVADGDTV
     YQPAVGQDDR GPVWLFSGQG SQWAAMGADL LTNESVFAAT VAELEPLIAA ESGFSVTEAM
     TAPETVTGID RVQPTIFAMQ VALAATMAAY GVRPGAVIGH SMGESAAAVV AGVLSAEDGV
     RVICRRSKLM ATIAGSAAMA SVELPALAVQ SELTALGIDD VVVAVVTAPQ STVIAGGTES
     VRKLVDIWER RDVLARAVAV DVASHSPQVD PILDELIAAL ADLNPKAPEI PYYSATLFDP
     REAPACDARY WADNLRHTVR FSAAVRSALD DGYRVFAELS PHPLLTHAVD QIAGSVGMPV
     AALAGMRREQ PLPLGLRRLL TDLHNAGAAV DFSVLCPQGR LVDAPLPAWS HRFLFYDREG
     VDNRSPGGST VAVHPLLGAH VRLPEEPERH AWQADVGTAT LPWLGDHRIH NVAALPGAAY
     CEMALSAARA VLGEQSEVRD MRFEAMLLLD DQTPVSTVAT VTSPGVVDFA VEALQEGVGH
     HLRRASAVLQ QVSGECEPPA YDMASLLEAH PCRVDGEDLR RQFDKHGVQY GPAFTGLAVA
     YVAEDATATM LAEVALPGSI RSQQGLYAIH PALLDACFQS VGAHPDSQSV GSGLLVPLGV
     RRVRAYAPVR TARYCYTRVT KVELVGVEAD IDVLDAHGTV LLAVCGLRIG TGVSERDKHN
     RVLNERLLTI EWHQRELPEM DPSGAGKWLL ISDCAASDVT ATRLADAFRE HSAACTTMRW
     PLHDDQLAAA DQLRDQVGSD EFSGVVVLTG SNTGTPHQGS ADRGAEYVRR LVGIARELSD
     LPGAVPRMYV VTRGAQRVLA DDCVNLEQGG LRGLLRTIGA EHPHLRATQI DVDEQTGVEQ
     LARQLLATSE EDETAWRDNE WYVARLCPTP LRPQERRTIV ADHQQSGMRL QIRTPGDMQT
     IELAAFHRVP PGPGQIEVAV RASSVNFADV LIAFGRYPSF EGHLPQLGTD FAGVVTAVGP
     GVTDHKVGDH VGGMSPNGCW GTFVTCDARL AATLPPGLGD AQAAAVTTAH ATAWYGLHEL
     ARIRAGDTVL IHSGTGGVGQ AAIAIARAAG AEIFATAGTP QRRELLRNMG IEHVYDSRSI
     EFAEQIRRDT NGRGVDVVLN SVTGAAQLAG LKLLAFRGRF VEIGKRDIYG DTKLGLFPFR
     RNLSFYAVDL GLLSATHPEE LRDLLGTVYR LTAAGELPMP QSTHYPLVEA ATAIRVMGNA
     EHTGKLVLHI PQTGKSLVTL PPEQAQVFRP DGSYIITGGL GGLGLFLAEK MAAAGCGRIV
     LNSRTQPTQK MRETIEAIAA MGSEVVVECG DIAQPGTAER LVATAVATGL PVRGVLHAAA
     VVEDATLANI TDELLARDWA PKVHGAWELH EATSGQPLDW FCLFSSAAAL TGSPGQSAYS
     AANSWLDAFA HWRQAQGLPA TAIAWGAWSD IGQLGWWSAS PARASALEES NYTAITPDEG
     AYAFEALLRH NRVYTGYAPV IGAPWLVAFA ERSRFFEVFS SSNGSGTSKF RVELNELPRD
     EWPARLRQLV AEQVSLILRR TVDPDRPLPE YGLDSLGALE LRTRIETETG IRLAPKNVSA
     TVRGLADHLY EQLAPDDAPA AALSSQ