L-Asparaginase from Penicillium sizovae Produced by a Recombinant Komagataella phaffii Strain

L-asparaginase is an important enzyme in the pharmaceutical field used as treatment for acute lymphoblastic leukemia due to its ability to hydrolyze L-asparagine, an essential amino acid synthesized by normal cells, but not by neoplastic cells. Adverse effects of L-asparaginase formulations are associated with its glutaminase activity and bacterial origin; therefore, it is important to find new sources of L-asparaginase produced by eukaryotic microorganisms with low glutaminase activity. This work aimed to identify the L-asparaginase gene sequence from Penicillium sizovae, a filamentous fungus isolated from the Brazilian Savanna (Cerrado) soil with low glutaminase activity, and to biosynthesize higher yields of this enzyme in the yeast Komagataella phaffii. The L-asparaginase gene sequence of P. sizovae was identified by homology to L-asparaginases from species of Penicillium of the section Citrina: P. citrinum and P. steckii. Partial L-asparaginase from P. sizovae, lacking the periplasmic signaling sequence, was cloned, and expressed intracellularly with highest enzymatic activity achieved by a MUT(+) clone cultured in BMM expression medium; a value 5-fold greater than that obtained by native L-asparaginase in P. sizovae cells. To the best of our knowledge, this is the first literature report of the heterologous production of an L-asparaginase from a filamentous fungus by a yeast

The translational gap for gene therapies in low- and middle-income countries

Gene therapy is at the forefront of modern medicine. Operating at the genomic level, these sophisticated technologies are designed to address the root cause of disease. This class of medicines is made possible by advances in genetic engineering and cellular delivery technologies. As scientific understanding behind disease prevention, diagnosis, and treatment improves in tandem with technological innovation, gene therapies will hopefully become safe and effective treatment options for a wide range of genetic and non-genetic diseases. However, as the medicinal scope of gene therapies expands, consideration must be given to who will benefit and what proactive steps must be taken to widen development and access potential, particularly in areas carrying high burden diseases likely to benefit from their introduction