Production of L-asparaginase from Candida utilis by solid-state fermentation: a comprehensive assessment of its antiproliferative potential on glioblastoma cells


Alkış M. D. Ö., İpek S. L., Tülek A., Gündüz C. P. B., Göktürk D.

World Journal of Microbiology and Biotechnology, vol.41, no.12, 2025 (SCI-Expanded, Scopus) identifier identifier

  • Publication Type: Article / Article
  • Volume: 41 Issue: 12
  • Publication Date: 2025
  • Doi Number: 10.1007/s11274-025-04638-7
  • Journal Name: World Journal of Microbiology and Biotechnology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, ABI/INFORM, BIOSIS, Compendex, Environment Index, MEDLINE
  • Keywords: Antiproliferative, Candida utilis, Glioblastoma, L-asparaginase, Solid state fermentation
  • Kütahya Health Sciences University Affiliated: Yes

Abstract

L-asparaginase (L-ASNase) is an enzyme that depletes asparagine, a key amino acid for cancer cell survival, producing aspartic acid and ammonia. Beyond its food industry applications, L-ASNase is a clinically important agent against acute lymphoblastic leukemia (ALL). In this study, L-ASNase was produced and purified from Candida utilis via solid-state fermentation. Optimization on wheat bran identified 2 mL inoculation volume, 60% moisture, and a 4-day fermentation period as the optimal conditions, yielding 172.5 U/mL activity. The purified enzyme was tested against glioblastoma (GBM) cell lines, showing IC₅₀ values of 0.4 U/mL for U87MG and 1.8 U/mL for T98G, with minimal toxicity toward normal HaCaT cells. Apoptotic effects were confirmed by DAPI/F-actin and Giemsa staining, while wound healing and clonogenic assays revealed inhibition of cell migration and colony formation. RT-qPCR analysis demonstrated downregulation of the Survivin gene, a key survival regulator. These findings highlight L-ASNase’s potent antiproliferative, anti-migratory, and pro-apoptotic effects, underscoring its potential as an adjuvant therapy for GBM.