L-asparaginase: a review of microbial production and protein engineering with translational applications for oncology and food safety.

L-Asparaginase (LA; EC 3.5.1.1) is a clinically and industrially relevant enzyme that hydrolyzes L-asparagine to L-aspartate and ammonia. LA has demonstrated efficacy as a chemotherapeutic agent by depleting L-asparagine, an amino acid essential for leukemic cell survival. FDA-approved formulations derived from Escherichia coli and Erwinia chrysanthemi face challenges, including a short half-life and adverse side effects, necessitating continuous efforts to develop more stable and specific variants. Concurrently, LA's role in acrylamide mitigation during food processing has garnered attention, supported by thermostable and high-yield fungal and bacterial strains. This review provides a comprehensive overview of LA's multifaceted roles, highlighting its therapeutic significance in treating acute lymphoblastic leukemia (ALL) and its role in acrylamide mitigation during food processing. It highlights exciting developments in the field, from discovering novel microbial sources to engineering the enzyme for improved performance. It also examines scalable production methodologies like submerged and solid-state fermentation, which are key to meeting growing demand. The review also highlights innovative strategies such as structural modifications and immobilization techniques aimed at enhancing enzyme stability, substrate specificity and therapeutic efficacy. This review demonstrates the transformative potential of LA in both healthcare and industrial contexts through integrating recent breakthroughs and innovative approaches. The insights provided aim to guide future research and innovation, paving the way for the development of optimized and sustainable applications of this crucial enzyme.

© 2025. The Author(s), under exclusive licence to Springer Nature B.V.