Inhibiting dihydrodipicolinate synthase across species: Towards specificity for pathogens?

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Abstract

Dihydrodipicolinate synthase (DHDPS) is a key enzyme in lysine biosynthesis and an important antibiotic target. The specificity of a range of heterocyclic product analogues against DHDPS from three pathogenic species, Bacillus anthracis, Mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus, and the evolutionarily related N-acetylneuraminate lyase, has been determined. The results suggest that the development of species-specific inhibitors of DHDPS as potential antibacterials is achievable.

Graphical abstract

Inhibitors of dihydrodipicolinate synthase (DHDPS), a key enzyme in lysine biosynthesis and an important antibiotic target, display significant species-specificity.

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Acknowledgments

This work was funded in part by the Australian Research Council (LX0776388 and DP0770888) and in part by the Royal Society of New Zealand Marsden Fund (contract UOC303).

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