The growing number of multidrug-resistant pathogenic bacteria is becoming a world leading challenge for the scientific community and for public health. However, advances in high-throughput technologies and whole-genome sequencing of bacterial pathogens make the construction of bacterial genome-scale metabolic models (GEMs) increasingly realistic. The use of GEMs as an alternative platforms will expedite identification of novel unconditionally essential genes and enzymes of target organisms with existing and forthcoming GEMs. This approach will follow the existing protocol for construction of high-quality GEMs, which could ultimately reduce the time, cost and labor-intensive processes involved in identification of novel antimicrobial drug targets in drug discovery pipelines. We discuss the current impact of existing GEMs of selected multidrug-resistant pathogenic bacteria for identification of novel antimicrobial drug targets and the challenges of closing the gap between genome-scale metabolic modeling and... Graphical abstract

L-2-Haloacid dehalogenase (DehL) from Rhizobium sp. RC1 is a stereospecific enzyme that acts exclusively on l-isomers of 2-chloropropionate and dichloroacetate. The amino acid sequence of this enzyme is substantially different from those of other l-specific dehalogenases produced by other organisms. DehL has not been crystallised, and hence its three-dimensional structure is unavailable. Herein, we review what is known concerning DehL and tentatively identify the amino acid residues important for catalysis based on a comparative structural and sequence analysis with well-characterised l-specific dehalogenases.

Dehalogenases are of high interest due to their potential applications in bioremediation and in synthesis of various industrial products. DehL is an L-2-haloacid dehalogenase (EC 3.8.1.2) that catalyses the cleavage of halide ion from L-2-halocarboxylic acid to produce D-2-hydroxycarboxylic acid. Although DehL utilises the same substrates as the other L-2-haloacid dehalogenases, its deduced amino acid sequence is substantially different (<25%) from those of the rest L-2-haloacid dehalogenases. To date, the 3D structure of DehL is not available. This limits the detailed understanding of the enzyme’s reaction mechanism. The present work predicted the first homology-based model of DehL and defined its active site. The monomeric unit of the DehL constitutes α/β structure that is organised into two distinct structural domains: main and subdomains. Despite the sequence disparity between the DehL and other L-2-haloacid dehalogenases, its structural model share similar fold as the experimentally solved L-DEX and DehlB structures. The findings of the present work will play a crucial role in elucidating the molecular details of the DehL functional mechanism.

Persistent evolution of multidrug resistance bacteria due to inappropriate use of conventional antibiotics is undermining treatment intervention for infectious diseases, thus constituting substantial proportion of the global public health problem. This, necessitated the search and development of new drugs particularly from plant origin that are effective against such superbugs. Therefore, the present study was designed to determine the phytochemical constituents in Sida acuta and their antibacterial effects on pathogenic bacterial species of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis. The phytochemical components of the extract were identified using standard methods. Furthermore, the antibacterial activity of the leaf extract against the bacterial pathogens were assessed using agar well diffusion and broth dilution method, at varying concentrations of the extract (37.50, 75, 150 and 300 mg/ml), and using Commercially obtained ciprofloxacin as control. Preliminary screening revealed that ethanolic leaf extract possesses many secondary metabolites such as alkaloids, flavonoids, phenol, tannins, terpenoids, glycosides and cardiac glycosides. The extract exhibited significant inhibitory effects at (p