The tale of a versatile enzyme: Molecular insights into keratinase for its industrial dissemination

Keratinases are unique among proteolytic enzymes for their ability to degrade recalcitrant insoluble proteins, and they are of critical importance in keratin waste management. Over the past few decades, researchers have focused on discovering keratinase producers, as well as producing and characterizing keratinases. The application potential of keratinases has been investigated in the feed, fertilizer, leathering, detergent, cosmetic, and medical industries. However, the commercial availability of keratinases is still limited due to poor productivity and properties, such as thermostability, storage stability and resistance to organic reagents. Advances in molecular biotechnology have provided powerful tools for enhancing the production and functional properties of keratinase. This critical review systematically summarizes the application potential of keratinase, and in particular certain newly discovered catalytic capabilities. Furthermore, we provide comprehensive insight into mechanistic and molecular aspects of keratinases including analysis of gene sequences and protein structures. In addition, development and current advances in protein engineering of keratinases are summarized and discussed, revealing that the engineering of protein domains such as signal peptides and pro-peptides has become an important strategy to increase production of keratinases. Finally, prospects for further development are also proposed, indicating that advanced protein engineering technologies will lead to improved and additional commercial keratinases for various industrial applications.