IUBMB Enzyme Nomenclature

EC 2.3.1.261

Accepted name: 4-hydroxyphenylalkanoate synthase

Reaction: (1) 4-hydroxybenzoyl-[4-hydroxyphenylalkanoate synthase] + 8 malonyl-CoA + 16 NADPH + 16 H+ = 17-(4-hydroxyphenyl)heptadecanoyl-[4-hydroxyphenylalkanoate synthase] + 8 CO2 + 8 CoA + 16 NADP+ + 8 H2O
(2) 4-hydroxybenzoyl-[4-hydroxyphenylalkanoate synthase] + 9 malonyl-CoA + 18 NADPH + 18 H+ + holo-[4-hydroxyphenylalkanoate synthase] = 19-(4-hydroxyphenyl)nonadecanoyl-[4-hydroxyphenylalkanoate synthase] + 9 CO2 + 9 CoA + 18 NADP+ + 9 H2O

Other name(s): msl7 (gene name); Pks15/1

Systematic name: malonyl-CoA:4-hydroxybenzoyl-[4-hydroxyphenylalkanoate synthase] malonyltransferase (4-hydroxyphenylalkanoate-forming)

Comments: 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-hydroxyphenylalkanoate 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.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Sirakova, T.D., Thirumala, A.K., Dubey, V.S., Sprecher, H. and Kolattukudy, P.E. The Mycobacterium tuberculosis pks2 gene encodes the synthase for the hepta- and octamethyl-branched fatty acids required for sulfolipid synthesis. J. Biol. Chem. 276 (2001) 16833-16839. [PMID: 11278910]

2. Constant, P., Perez, E., Malaga, W., Laneelle, M.A., Saurel, O., Daffe, M. and Guilhot, C. 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. J. Biol. Chem. 277 (2002) 38148-38158. [PMID: 12138124]

3. Simeone, R., Leger, M., Constant, P., Malaga, W., Marrakchi, H., Daffe, M., Guilhot, C. and Chalut, C. Delineation of the roles of FadD22, FadD26 and FadD29 in the biosynthesis of phthiocerol dimycocerosates and related compounds in Mycobacterium tuberculosis. FEBS J. 277 (2010) 2715-2725. [PMID: 20553505]

[EC 2.3.1.261 created 2017]


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