5.2 Improved biotemplate production yields
VLPs frequently form insoluble aggregates when expressed in non-native hosts that are unsuitable for biotemplating processes [87]. To increase the yield of usable VLP biotemplates, the solubility of heterologous CP must be enhanced. There are many ways to increase protein solubility [88]; however, increasing CP solubility for VLPs production is challenging as one of the drivers of protein insolubility, strong hydrophobic interactions, is also the driving force for virion and VLP assembly. However, machine learning algorithms have begun to identify the design rules for soluble VLP CP design without disrupting VLP self-assembly based on hydrophobicity scales [89]. An early report with these tools counterintuitively suggests that CP solubility may be highly correlated with arginine content in some VLPs, despite its negative correlation with solubility of short chain variable fragments. Arginine reduces many hydrophobic protein-protein interactions while interacting favorably with other amino acids to reduce random aggregation. However, these tools have yet to be applied to forward engineer novel VLP CPs.