KEGG   ENZYME: 2.3.1.261
Entry
EC 2.3.1.261                Enzyme                                 
Name
(4-hydroxyphenyl)alkanoate synthase;
msl7 (gene name);
Pks15/1
Class
Transferases;
Acyltransferases;
Transferring groups other than aminoacyl groups
Sysname
malonyl-CoA:4-hydroxybenzoyl-[(4-hydroxyphenyl)alkanoate synthase] malonyltransferase [(4-hydroxyphenyl)alkanoate-forming]
Reaction(IUBMB)
(1) 4-hydroxybenzoyl-[(4-hydroxyphenyl)alkanoate synthase] + 8 malonyl-CoA + 16 NADPH + 16 H+ = 17-(4-hydroxyphenyl)heptadecanoyl-[(4-hydroxyphenyl)alkanoate synthase] + 8 CO2 + 8 CoA + 16 NADP+ + 8 H2O [RN:R11615];
(2) 4-hydroxybenzoyl-[(4-hydroxyphenyl)alkanoate synthase] + 9 malonyl-CoA + 18 NADPH + 18 H+ + holo-[(4-hydroxyphenyl)alkanoate synthase] = 19-(4-hydroxyphenyl)nonadecanoyl-[(4-hydroxyphenyl)alkanoate synthase] + 9 CO2 + 9 CoA + 18 NADP+ + 9 H2O [RN:R11616]
Reaction(KEGG)
R11615 R11616
Substrate
4-hydroxybenzoyl-[(4-hydroxyphenyl)alkanoate synthase];
malonyl-CoA [CPD:C00083];
NADPH [CPD:C00005];
H+ [CPD:C00080];
holo-[(4-hydroxyphenyl)alkanoate synthase]
Product
17-(4-hydroxyphenyl)heptadecanoyl-[(4-hydroxyphenyl)alkanoate synthase];
CO2 [CPD:C00011];
CoA [CPD:C00010];
NADP+ [CPD:C00006];
H2O [CPD:C00001];
19-(4-hydroxyphenyl)nonadecanoyl-[(4-hydroxyphenyl)alkanoate synthase]
Comment
The enzyme is part of the biosynthetic pathway of phenolphthiocerol, a lipid that serves as a virulence factor of pathogenic mycobacteria. It catalyses the elongation of 4-hydroxybenzoate that is loaded on its acyl-carrier domain to form (4-hydroxyphenyl)alkanoate intermediates. The enzyme adds either 8 or 9 malonyl-CoA units, resulting in formation of 17-(4-hydroxyphenyl)heptadecanoate or 19-(4-hydroxyphenyl)nonadecanoate, respectively. As the enzyme lacks a thioesterase domain [1], the product remains loaded on the acyl-carrier domain at the end of catalysis, and has to be hydrolysed by an as-yet unknown mechanism.
History
EC 2.3.1.261 created 2017
Orthology
K12430  4-hydroxyphenylalkanoate synthase
Genes
BGLbglu_2p0600
MTURv2946c(pks1) Rv2947c(pks15)
MTVRVBD_2946c RVBD_2947c
MTCMT3018 MT3021.1
MRAMRA_2973(pks1) MRA_2974(pks15)
MTFTBFG_12960 TBFG_12961
MTBTBMG_01024 TBMG_01026
MTKTBSG_01032 TBSG_01034
MTZTBXG_001014 TBXG_003977
MTGMRGA327_18115 MRGA327_18120
MTIMRGA423_18300 MRGA423_18305 MRGA423_18310
MTECCDC5079_2706
MTURCFBS_3105(pks1)
MTLCCDC5180_2670 CCDC5180_2671
MTOMTCTRI2_3004(pks1) MTCTRI2_3005(pks15)
MTDUDA_2946c(pks1) UDA_2947c(pks15)
MTNERDMAN_3229(pks1) ERDMAN_3230(pks15)
MTJJ112_15770 J112_15775
MTUBMT7199_2981 MT7199_2982
MTUCJ113_20515 J113_20525
MTUEJ114_15735 J114_15740
MTULTBHG_02876 TBHG_02877
MTUTHKBT1_3093(pks1)
MTUUHKBT2_3098(pks1)
MTQHKBS1_3100(pks1)
MBOBQ2027_MB2971C(pks1)
MBBBCG_2968c(pks1)
MBTJTY_2963(pks1)
MBMBCGMEX_2963c(pks1)
MBKK60_030530
MBXBCGT_2784
MAFMAF_29520(pks)
MMICRN08_3249
MCEMCAN_29661(pks1) MCAN_29671(pks15)
MCQBN44_60422(pks)
MCVBN43_40654
MCXBN42_40946
MCZBN45_51358(pks)
MLEML0135
MLBMLBr00135
MMANMMAN_09060(pks15_1)
MULMUL_2005(pks15_1)
MMIMMAR_0101 MMAR_1762(pks15_1) MMAR_3099 MMAR_3796
MMAEMMARE11_00900 MMARE11_16810(pks15_1) MMARE11_30210
MLIMULP_05771(pks15_1)
MKNMKAN_23955
MHADB586_03310
MKUI2456_12290
MCOOMCOO_14800(pks15_1)
MBAIMB901379_01072 MB901379_01577 MB901379_02742
MPSEMPSD_40740(pks15_1)
MSHOMSHO_11670(pks1) MSHO_37290 MSHO_54810(pks15_1)
MLJMLAC_28850(pks15_1)
MSHJMSHI_07230(pks15_1) MSHI_15430(pks7_1)
MMAMK3U93_11415
MSPGF6B93_10350
MOTLTS72_16045
MLMMLPF_0163(pks1_15)
MAUBMAUB_28870
NHUH0264_30735
SRCM271_40690
SBHSBI_01984
SALUDC74_7916
SGSAVL59_15435
SALFSMD44_07596
PSEAWY02_28925
PHHAFB00_29720(selK) AFB00_29775(selJ)
PFLAPflav_008130 Pflav_008290 Pflav_056820 Pflav_057000 Pflav_057010
PSUUPsuf_016590(pks15_1_1) Psuf_016650 Psuf_018900
 » show all
Reference
1  [PMID:11278910]
  Authors
Sirakova TD, Thirumala AK, Dubey VS, Sprecher H, Kolattukudy PE
  Title
The Mycobacterium tuberculosis pks2 gene encodes the synthase for the hepta- and octamethyl-branched fatty acids required for sulfolipid synthesis.
  Journal
J Biol Chem 276:16833-9 (2001)
DOI:10.1074/jbc.M011468200
Reference
2  [PMID:12138124]
  Authors
Constant P, Perez E, Malaga W, Laneelle MA, Saurel O, Daffe M, Guilhot C
  Title
Role of the pks15/1 gene in the biosynthesis of phenolglycolipids in the Mycobacterium tuberculosis complex. Evidence that all strains synthesize glycosylated p-hydroxybenzoic methyl esters and that strains devoid of phenolglycolipids harbor a frameshift mutation in the pks15/1 gene.
  Journal
J Biol Chem 277:38148-58 (2002)
DOI:10.1074/jbc.M206538200
  Sequence
Reference
3  [PMID:20553505]
  Authors
Simeone R, Leger M, Constant P, Malaga W, Marrakchi H, Daffe M, Guilhot C, Chalut C
  Title
Delineation of the roles of FadD22, FadD26 and FadD29 in the biosynthesis of phthiocerol dimycocerosates and related compounds in Mycobacterium tuberculosis.
  Journal
FEBS J 277:2715-25 (2010)
DOI:10.1111/j.1742-464X.2010.07688.x
Other DBs
ExplorEnz - The Enzyme Database: 2.3.1.261
IUBMB Enzyme Nomenclature: 2.3.1.261
ExPASy - ENZYME nomenclature database: 2.3.1.261
BRENDA, the Enzyme Database: 2.3.1.261

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