Microbial carbohydrate-binding toxins – From etiology to biotechnological application
Natalia Danielewicz, Francesca Rosato, Wenyue Dai, Winfried Römer, W. Bruce Turnbull, Juergen Mairhofer
Abstract
Glycan-recognizing toxins play a significant role in the etiology of many diseases afflicting humanity. The carbohydrate recognition domains of these toxins play essential roles in the virulence of many microbial organisms with multiple modes of action, from promoting pore formation to facilitating the entry of toxic enzymatic subunits into the host cell. Carbohydrate-binding domains with an affinity for specific glycan-based receptors can also be exploited for various applications, including detecting glycobiomarkers, as drug delivery systems, and new generation biopharmaceutical products and devices (e.g. glycoselective capture of tumor-derived exosomes). Therefore, understanding how to efficiently express and purify recombinant toxins and their carbohydrate-binding domains can enable opportunities for the formulation of innovative biopharmaceuticals that can improve human health. Here, we provide an overview of carbohydrate-binding toxins in the context of biotechnological innovation. We review 1) structural characteristics concerning the toxins' mode of action; 2) applications and therapeutic design with a particular emphasis on exploiting carbohydrate-binding toxins for production of anti-tumor biopharmaceuticals; discuss 3) possible ways to manufacture those molecules at a bioreactor scale using microbial expression systems, and 4) their purification using their affinity for glycans.