The Asparaginase Database: a comprehensive resource and classification of l-asparaginases

l-Asparaginases have been essential anticancer biopharmaceuticals for nearly half a century, particularly in the treatment of acute lymphoblastic leukaemia. Despite their success, current preparations face challenges, such as strong immunogenicity, reduced stability, and secondary l-glutaminase activity. Systematic discovery and engineering of l-asparaginases with desirable properties are hindered by the limitations of existing l-asparaginase classifications being unable to keep pace with rapid sequence discovery or not reflecting the growing diversity of l-asparaginase characteristics. We present The Asparaginase Database, a resource for curated l-asparaginase sequences, conserved motifs, structures, and experimental data organised by a sequence similarity driven classification into 40 phylogenetic families and 14 clans within previously established l-asparaginase classes. This framework provides a new model for the classification of l-asparaginases based on large-scale molecular phylogeny and could enable researchers to navigate l-asparaginase diversity and identify promising candidates for therapeutic development. Database URL:  https://asparaginasedb.com/.