Prokaryotic ATP-binding cassette type F proteins in overcoming ribosomal stalling: mechanisms, evolution, and perspective for applications in bio-manufacturing.

This article focuses on prokaryotic ATP-binding cassette type F (ABCF) proteins and their dual roles in overcoming ribosomal stalling during translation and conferring antibiotic resistance. It distinguishes between antibiotic resistance ABCF (ARE-ABCF) proteins, which protect ribosomes from antibiotics by binding to the ribosomal E site and inducing structural changes to prevent drug binding, and housekeeping ABCF proteins, such as YfmR and YkpA in *Bacillus subtilis*, which resolve intrinsic translation challenges caused by difficult-to-translate sequences like proline-rich or charged amino acid motifs without conferring antibiotic resistance. Phylogenetic analyses reveal evolutionary divergence between these groups, with some ARE-ABCF proteins like PoxtA representing transitional forms. The review highlights recent structural and functional studies elucidating these proteins' mechanisms and discusses their potential applications in bio-manufacturing to improve the production of proteins containing challenging motifs.