Proteins play a pivotal role across various industries, from food/feed to biocatalysts and life-saving therapeutics. However, the transition from natural functions to industrial applications often presents formidable obstacles. Nature has evolved proteins for its own purposes, which can lead to problems if they are used for commercial applications: Enzymes do not recognize the target substrate or produce undesired side-products; solvents inactivate them, or they precipitate because of unfavorable process conditions. Some biotherapeutics are recognized as foreign molecules by the immune system, while others have low affinity, and some are so small that they are too rapidly cleared from the bloodstream before exerting an effect. Expression and purification challenges further exacerbate these complexities, hindering or destroying any hopes of commercialization. Traditional approaches may offer no cost-efficient solution since they rely on laborious experimentation, and limited data sets.