A novel class of oligoarylamide antibiotics defined by albicidins and cystobactamids

Abstract

Covering: 2014/2015 up to 2025.

The global rise of antimicrobial resistance imposes a strong demand to develop new antibacterial drugs, and microbes have been a prime source for their discovery. Albicidins and cystobactamids, isolated from xanthomonadaceae and myxococcaceae, respectively, span a novel class of oligoarylamide antibiotics with a unique chemical scaffold featured by para-aminobenzoic acid building blocks. Both compounds exhibit broad spectrum and potent activity against Gram-positive and Gram-negative pathogens through inhibiting DNA gyrase and topoisomerase IV. This article summarizes the insights gained on this class since its initial disclosure in 2014/2015 up to 2025. It discusses natural derivatives, their biosynthesis and chemical synthesis, the unique binding mode to DNA gyrase, and systematic medicinal chemistry programs with >700 analogs that led to resistance-breaking antibiotics with in vivo efficacy. The review illustrates the importance of natural product research to address the global need for new antibiotics.