biostudies-literatureRigouin CBLRD VANIBIB NIH HHS10224https://www.ebi.ac.uk/biostudies/studies/S-EPMC5579231biostudies-literatureUnknown7(1)L-asparaginase is a chemotherapy drug used to treat acute lymphoblastic leukemia (ALL). The main prerequisite for clinical efficacy of L-asparaginases is micromolar K_M for asparagine to allow for complete depletion of this amino acid in the blood. Since currently approved L-asparaginases are of bacterial origin, immunogenicity is a challenge, which would be mitigated by a human enzyme. However, all human L-asparaginases have millimolar K_M for asparagine. We recently identified the low K_M guinea pig L-asparaginase (gpASNase1). Because gpASNase1 and human L-asparaginase 1 (hASNase1) share ~70% amino-acid identity, we decided to humanize gpASNase1 by generating chimeras with hASNase1 through DNA shuffling. To identify low K_M chimeras we developed a Scientific reportsDiscovery of human-like L-asparaginases with potential clinical use by directed evolution.PMC5579231I01 BX001919R01 EB013685Schalk AMLavie ARigouin CNguyen HAfalseDiscovery of human-like L-asparaginases with potential clinical use by directed evolution.L-asparaginase is a chemotherapy drug used to treat acute lymphoblastic leukemia (ALL). The main prerequisite for clinical efficacy of L-asparaginases is micromolar K_M for asparagine to allow for complete depletion of this amino acid in the blood. Since currently approved L-asparaginases are of bacterial origin, immunogenicity is a challenge, which would be mitigated by a human enzyme. However, all human L-asparaginases have millimolar K_M for asparagine. We recently identified the low K_M guinea pig L-asparaginase (gpASNase1). Because gpASNase1 and human L-asparaginase 1 (hASNase1) share ~70% amino-acid identity, we decided to humanize gpASNase1 by generating chimeras with hASNase1 through DNA shuffling. To identify low K_M chimeras we developed a 2017-01-01T00:00:00Z2017 Aug2026-05-04T06:32:36.296Z2019-03-27T02:55:08ZS-EPMC55792312886048010.1038/s41598-017-10758-4