Editorial: Protein Solubility and Aggregation in Bacteria

For many years, the aggregation of proteins and polypeptides remained a neglected area of protein chemistry. It was only with the discovery that the insoluble deposits found in the organs and tissues of patients suffering from different diseases were enriched in a single, but different polypeptide, that the interest in understanding how and why these proteins aggregate arose (Fernàndez-Busquets et al., 2008). From that time on, the study of protein aggregation has evolved to become a key research topic, whose implications span disciplines like biochemistry, biomedicine, biotechnology, and nanotechnology. The formation of insoluble protein aggregates is linked to more than 40 human diseases (Invernizzi et al., 2012). In all these disorders, the aggregated proteins assemble into a common β-sheet enriched supra-molecular structure, known as amyloid. A large number of higher eukaryotic biochemical pathways, from DNA replication to protein degradation, have been modeled first in prokaryotic organisms, providing important clues on the molecular basis of pathology (Dwyer et al., 2012). Scientists have long known that, very often, the heterologous expression of proteins in bacteria results in the accumulation of the target protein in insoluble deposits. However, only recently a number of laboratories have dared to exploit this well-characterized phenomenon to dissect the determinants of protein aggregation into amyloid assemblies (Villar-Pique and Ventura, 2012). Bacteria posses an intracellular environment that, while differing from that of eukaryotic cells, is physiologically more relevant than a test tube. Accordingly, they constitute privileged model systems to understand the mechanisms behind amyloid assembly and the cellular fitness cost associated with the formation of these aggregates (Navarro et al., 2014), but also to screen for effective modulators of amyloid aggregation with potential therapeutic applications (Villar-Piqué et al., 2012). Protein aggregation constitutes a major bottleneck in the biotechnological production of protein based therapeutics. Consequently, a large effort has been devoted to the development of orthogonal strategies to increase soluble protein yields, including in vitro protein synthesis (Ventura, 2005). Bacterial extracts have become a convenient means to produce recombinant proteins in vitro, because they contain all the machinery required for protein synthesis. This technology has rendered a significant volume of data on the behavior of proteins during their cell-free synthesis. As illustrated by Tokmakov, these datasets can be exploited to derive the physicochemical and structural properties associated with the solubility and aggregation of eukaryotic proteins