Engineering nucleation/crystallization to intensify the enzymatic reactions and fermentation: A review

• Strategy engineering nucleation/crystallization in enzymatic reactions is reviewed. • Several cases about external and internal crystallization are summarized. • Enzymatic reactive crystallization is useful to avoid product inhibition. • Integration of crystallization and reaction is applicable in fermentation. • Perspectives and challenges on crystallization and bioprocess are discussed. Bioprocess such as enzymatic reaction and fermentation have experienced fast development as green and sustainable techniques, which can integrate with different separating unit operations for better performance, such as crystallization. Here we reviewed the application of crystallization in intensifying enzymatic reactions and fermentation process in the perspective of nucleation implementation and crystallization process control. Since the properties of free enzyme, immobilized enzyme, catalytic cell, microorganism etc. were different, the accomplishment of crystallization was not unique. Specifically, temperature difference, seeds, crystallization agents, electric field, co-crystal formers etc. have been used to induce nucleation/crystallization in bioprocess. How these methods can be effectively integrated with enzymatic reactions and fermentation was our original concern. Thus various ways to induce nucleation or maintain supersaturation were discussed in representative examples. The hybrid process design and control were emphasized, and the key operating parameters were highlighted.