Similar to its eukaryotic counterpart, the prokaryotic cytoskeleton is essential for the structural and mechanical properties of bacterial cells. The essential protein FtsZ is a central player in the cytoskeletal family, forms a cytokinetic ring at mid-cell, and recruits the division machinery to orchestrate cell division. Cells depleted of or lacking functional FtsZ do not divide and grow into long filaments that eventually lyse. FtsZ has been studied extensively as a target for antibacterial development. In this Perspective, we review the structural and biochemical properties of FtsZ, its role in cell biochemistry and physiology, the different mechanisms of inhibiting FtsZ, small molecule antagonists (including some misconceptions about mechanisms of action), and their discovery strategies. This collective information will inform chemists on different aspects of FtsZ that can be (and have been) used to develop successful strategies for devising new families of cell division inhibitors.

The bacterial cell division protein FtsZ is one of many potential targets for the development of novel antibiotics. Recently, zantrin Z3 was shown to be a cross-species inhibitor of FtsZ; however, its specific interactions with the protein are still unknown. Herein we report the synthesis of analogues that contain a more tractable core structure and an analogue with single-digit micromolar inhibition of FtsZ's GTPase activity, which represents the most potent inhibitor of Escherichia coli FtsZ reported to date. In addition, the zantrin Z3 core has been converted to two potential photo-cross-linking reagents for proteomic studies that could shed light on the molecular interactions between FtsZ and molecules related to zantrin Z3.

Bisavenanthramide B-6 (2) is a highly substituted γ-lactam derived from oat leaves. Development of a new base-promoted anhydride Mannich reaction with N-sulfonylated imines that forms the core structure of 2 in a single step is presented. Further elaboration allows for a facile one-pot double Buchwald N-arylation to install the final rings onto the densely substituted γ-lactam core. This route provides the natural product in a longest linear sequence of nine steps.

We strive to make chemistry more available and exciting for disabled scientists by developing accessible and safe methodologies to be employed by high school, undergraduate, and graduate students. We share philosophies and methods that were found to be effective in ensuring a safe laboratory environment. Namely, an accessible and safe chemistry laboratory requires assistance and extensive contributions from everyone involved. A discussion of technologies that make our computational chemistry laboratory accessible to blind and visually impaired (BVI) researchers follows. These recommendations are derived from our personal experiences with learning and teaching chemistry, with serving on a chemistry accessibility committee and with organizing and running chemistry camps for BVI students. In addition, we have begun work with sighted high school students who perform visual activities under blindfold. These experiences challenge the student under blindfold to learn how to function without all five senses while simultaneously training a sighted peer to safely and accurately assist with nonvisual cues.

The small molecule PC190723 was previously identified as an inhibitor of the cell division protein FtsZ in several Gram-positive bacteria. Here, we utilize genetic, chemical, and single-cell approaches to show that PC190723 is also effective in the Gram-negative bacterium Escherichia coli when outer membrane permeability is compromised, and that PC190723 blocks division through a previously unreported FtsZ-independent mechanism of action.