Microbial protein cell factories fight back?

The biopharmaceutical market is growing faster than ever, with two production systems competing for market dominance: mammalian cells and microorganisms. In recent years, based on the rise of antibody-based therapies, new biotherapeutic approvals have favored mammalian hosts. However, not only has extensive research elevated our understanding of microbes to new levels, but emerging therapeutic molecules also facilitate their use; thus, is it time for microbes to fight back? In this review, we answer this timely question by cross-comparing four microbial production hosts and examining the innovations made to both their secretion and post-translational modification (PTM) capabilities. Furthermore, we discuss the impact of tools, such as omics and systems biology, as well as alternative production systems and emerging biotherapeutics.