Targeting IspD for Anti-infective and Herbicide Development: Exploring Its Role, Mechanism, and Structural Insights

Antimicrobial resistance (AMR) and herbicide resistance pose threats to society, necessitating novel anti-infectives and herbicides exploiting untapped modes of action like inhibition of IspD, the third enzyme in the MEP pathway. The MEP pathway is essential for a wide variety of human pathogens, including Pseudomonas aeruginosa, Mycobacterium tuberculosis, and Plasmodium falciparum, as well as plants. Within the current perspective, we focused our attention on the third enzyme in this pathway, IspD, offering a comprehensive summary of the reported modes of inhibition and common trends, with the goal to inspire future research dedicated to this underexplored target. In addition, we included an overview of the history, catalytic mechanism, and structure of the enzyme to facilitate access to this attractive target.