LAUSR

Today, the availability of methods for the activity‐preserving and cost‐efficient downstream processing of enzymes forms a major bottleneck to the use of these valuable tools in technical processes. A promising technology appears to be foam fractionation, which utilizes the adsorption of proteins at a gas–liquid interface. However, the employment of surfactants and the dependency of the applicability on individual properties of the target molecules are considerable drawbacks. Here, we demonstrate that a reversible fusion of the large, surface‐active protein Ranaspumin‐2 (Rsn‐2) to a β‐lactamase (Bla) enabled both surfactant‐free formation of a stable foam and directed enrichment of the enzyme by the foaming. At the same time, Bla maintained 70% of its catalytic activity, which was in stark contrast to the enzyme without fusion to Rsn‐2. Rsn‐2 predominantly mediated adsorption. Comparable results were obtained after fusion to the structurally more complex penicillin G acylase (PGA) as the target enzyme. The results indicate that using a surface‐active protein as a fusion tag might be the clue to the establishment of foam fractionation as a general method for enzyme downstream processing.