The present invention relates to improved methods for protein purification of high-value heterologous proteins by providing fusion proteins suitable for affinity purification and improved and economical methods of proteolytic cleavage of fusion proteins. The methods are useful for large-scale production of purified recombinant proteins from plants, plant-derived tissue or plant cells. The invention aims to reduce the cost and improve the quality of downstream processing of heterologous proteins produced in plants and other biological production systems.