Laboratory of Medical Biotechnology, Institute of Biomedical Chemistry, Pogodinskaya St. 10/8, 119121 Moscow, Russia.
Department of Biochemistry, Peoples' Friendship University of Russia named after Patrice Lumumba (RUDN University), Miklukho-Maklaya St. 6, 117198 Moscow, Russia.
Int J Mol Sci. 2023 Oct 16;24(20):15220. doi: 10.3390/ijms242015220.
Genetic engineering for heterologous expression has advanced in recent years. Model systems such as , and are often used as host microorganisms for the enzymatic production of L-asparaginase, an enzyme widely used in the clinic for the treatment of leukemia and in bakeries for the reduction of acrylamide. Newly developed recombinant L-asparaginase (L-ASNase) may have a low affinity for asparagine, reduced catalytic activity, low stability, and increased glutaminase activity or immunogenicity. Some successful commercial preparations of L-ASNase are now available. Therefore, obtaining novel L-ASNases with improved properties suitable for food or clinical applications remains a challenge. The combination of rational design and/or directed evolution and heterologous expression has been used to create enzymes with desired characteristics. Computer design, combined with other methods, could make it possible to generate mutant libraries of novel L-ASNases without costly and time-consuming efforts. In this review, we summarize the strategies and approaches for obtaining and developing L-ASNase with improved properties.
近年来,异源表达的基因工程取得了进展。 、 和 等模型系统通常被用作酶法生产 L-天冬酰胺酶的宿主微生物,该酶广泛用于临床治疗白血病和面包店降低丙烯酰胺含量。 新开发的重组 L-天冬酰胺酶(L-ASNase)可能对天冬酰胺的亲和力低、催化活性降低、稳定性低、谷氨酰胺酶活性或免疫原性增加。 现在有一些成功的 L-ASNase 商业制剂。 因此,获得具有适合食品或临床应用的改进特性的新型 L-ASNase 仍然是一个挑战。 合理设计和/或定向进化与异源表达的结合已被用于创建具有所需特性的酶。 计算机设计与其他方法相结合,可以在不花费大量时间和精力的情况下生成新型 L-ASNase 的突变文库。 在这篇综述中,我们总结了获得和开发具有改进特性的 L-ASNase 的策略和方法。