Enzymes (3r) - hydroxyacyl - pca involved in the biosynthesis of mycolic acids and their use for the screening of antibiotics

摘要

(3R)-hydroxyacyl-ACP dehydratase enzymes (I) involved in the FAS-II system of mycobacteria are new. Enzymes (I) involved in the FAS-II system of mycobacteria are in the form of homodimers or homomultimers comprising two or more proteins comprising a hydrolase 2 unit of formula (II) or a a related catalytic unit of formula (III), or in the form of heterodimers or heteromultimers comprising a protein as above and a protein that lacks a hydrolase 2 unit but has a hotdog fold structure, and catalyze the hydration of (3R)-hydroxyacyl compounds of formula (IV) to 2-trans-enoyl compounds of formula (V) and/or catalyze the hydration of (V) to (IV). [YF]-x(1,2)-[LIVG]-[STGC]-G-D-x-N-P-[LIV]-H-x(5)-[AS] (II) D-x(4)-H (III) CH 3(CH 2) n-CH(OH)-CH 2-CO-S-X (IV) CH 2(CH 2) n-CH=CH-CO-S-X (V) x(n) : n amino acids; X : ACP or CoA; n : 0 or more; amino acids in square brackets : are alternatives. Independent claims are also included for: (1) polynucleotides coding for (I); (2) expression vectors containing the polynucleotides; prokaryotic or eukaryotic host cells transformed with the polynucleotides or vectors; (3) producing (I) by culturing the cells; (4) inhibiting biosynthesis of mycolata envelope compounds by inhibiting the expression or activity of (I).