AI Article Synopsis
- L-asparaginase (ASNase) is a crucial drug for treating acute lymphoblastic leukemia (ALL), but existing bacterial versions can cause immune reactions.
- Researchers isolated 134 yeast strains from marine sediments in Antarctica and found nine that produce L-asparaginase without glutaminase, with CRM 1648 showing the highest activity.
- The optimal conditions for yeast growth and ASNase production were identified, suggesting that cold-adapted yeasts could provide a promising, low-side-effect alternative for commercial L-asparaginase production.
Article Abstract
L-asparaginase (ASNase) is an essential drug in the treatment of acute lymphoblastic leukemia (ALL). Commercial bacterial ASNases increase patient survival, but the consequent immunological reactions remain a challenge. Yeasts ASNase is closer to human congeners and could lead to lower side effects. Among 134 yeast strains isolated from marine-sediments in King George Island, Antarctica, nine were L-asparaginase producing yeasts and glutaminase-free. CRM 1648 yielded the highest ASNase activity (490.41 U.L) and volumetric productivity (5.12 U.L h). Sucrose, yeast extract and proline were the best carbon and nitrogen sources to support growth and ASNase production. A full factorial design analysis pointed the optimum media condition for yeast growth and ASNase yield: 20 g L sucrose, 15 g L yeast extract and 20 g L proline, which resulted in 4582.5 U L and 63.64 U L h of ASNase and volumetric productivity, respectively. Analysis of temperature, pH, inoculum and addition of seawater indicated the best condition for ASNase production by this yeast: 12-15 °C, pH 5.5-6.5 and seawater >25% (v/v). Inoculum concentration seems not to interfere. This work is pioneer on the production of ASNase by cold-adapted yeasts, highlighting the potential of these microbial resources as a source of glutaminase-free L-asparaginase for commercial purposes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1080/10826068.2020.1815053 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A human-like glutaminase-free asparaginase is highly efficacious in ASNS leukemia and solid cancer mouse xenograft models.
Cancer Lett
December 2024
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, USA; Enzyme By Design Inc., Chicago, USA; Research Biologist, Biological Science Research and Development, Department of Veterans Affairs Medical Center, Chicago, IL, USA. Electronic address:
L-asparaginase (L-ASNase) is crucial in treating pediatric acute lymphoblastic leukemia (ALL), but its use is hampered by side effects from the immunogenicity and L-glutaminase (L-GLNase) co-activity of FDA-approved bacterial L-ASNases, often leading to treatment discontinuation and poor outcomes. The toxicity of these L-ASNases makes them especially challenging to use in adult cancer patients. To overcome these issues, we developed EBD-200, a humanized guinea pig L-ASNase with low Km and no L-GLNase activity, eliminating glutamine-related toxicity.
View Article and Find Full Text PDFArtificial intelligence-based optimization for extracellular L-glutaminase free L-asparaginase production by Streptomyces violaceoruber under solid state fermentation conditions.
Sci Rep
November 2024
Botany and Microbiology Department, Faculty of Science, Arish University, Al-Arish, 45511, Egypt.
The bacterial L-asparaginase is a highly effective chemotherapeutic drug and a cornerstone of treatment protocols used for treatment the acute lymphoblastic leukemia in pediatric oncology. A potential actinomycete isolate, Streptomyces sp. strain NEAE-99, produces glutaminase-free L-asparaginase was isolated from a soil sample.
View Article and Find Full Text PDFL-Asparaginase from Lachancea Thermotolerans: Effect of Lys99Ala on Enzyme Performance and in vitro Antileukemic Efficacy.
Biotechnol J
November 2024
Department of Bioengineering, Gebze Technical University, Gebze, Kocaeli, Türkiye.
Article Synopsis
- L-asparaginases are enzymes that convert L-asparagine into L-aspartic acid and ammonia, and they are important in the pharmaceutical industry, particularly for cancer treatments.
- Scientists are exploring yeast-derived L-asparaginases as an alternative to bacterial ones, which can cause adverse immune responses.
- The study focuses on a specific yeast enzyme, Lachancea thermotolerans, demonstrating that a mutant form of this enzyme shows increased activity and significant antileukemic potential compared to commercial bacterial versions.
Rapid and comprehensive analysis of complex proteomes across large sample sets is vital for unlocking the potential of systems biology. We present UFP-MS, an ultra-fast mass spectrometry (MS) proteomics method that integrates narrow-window data-independent acquisition (nDIA) with short-gradient micro-flow chromatography, enabling profiling of >240 samples per day. This optimized MS approach identifies 6,201 and 7,466 human proteins with 1- and 2-min gradients, respectively.
View Article and Find Full Text PDFCharacterization of Glutaminase-Free Asparaginase (MSMEG_3173).
ACS Omega
September 2024
Laboratório de Genômica Funcionale Bioinformática, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-900, Brazil.
l-asparaginase is an enzyme catalyzing the hydrolysis of l-asparagine into l-aspartate and ammonia, which is of great therapeutic importance in tumor treatment. However, commercially available enzymes are associated with adverse effects, and searching for a new l-asparaginase with better pharmaceutical properties was the aim of this work. The coding sequence for l-asparaginase (MsA) was cloned and expressed.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!