Chemical Engineering Department, Universidad de la Frontera, Francisco Salazar 1145, 4811230, Temuco, Región de la Araucanía, Chile.
Departamento de Ciencias Básicas, Facultad de Ciencias, Universidad Santo Tomas, Santiago, Chile.
BioDrugs. 2023 Nov;37(6):793-811. doi: 10.1007/s40259-023-00622-5. Epub 2023 Sep 12.
Over the past few years, there has been a surge in the industrial production of recombinant enzymes from microorganisms due to their catalytic characteristics being highly efficient, selective, and biocompatible. L-asparaginase (L-ASNase) is an enzyme belonging to the class of amidohydrolases that catalyzes the hydrolysis of L-asparagine into L-aspartic acid and ammonia. It has been widely investigated as a biologic agent for its antineoplastic properties in treating acute lymphoblastic leukemia. The demand for L-ASNase is mainly met by the production of recombinant type II L-ASNase from Escherichia coli and Erwinia chrysanthemi. However, the presence of immunogenic proteins in L-ASNase sourced from prokaryotes has been known to result in adverse reactions in patients undergoing treatment. As a result, efforts are being made to explore strategies that can help mitigate the immunogenicity of the drug. This review gives an overview of recent biotechnological breakthroughs in enzyme engineering techniques and technologies used to improve anti-leukemic L-ASNase, taking into account the pharmacological importance of L-ASNase.
在过去的几年中，由于微生物来源的重组酶具有高效、高选择性和生物相容性的催化特点，其工业生产呈爆发式增长。L-天冬酰胺酶（L-ASNase）是一种属于酰胺水解酶类的酶，能够催化 L-天冬酰胺水解生成 L-天冬氨酸和氨。由于其具有抗肿瘤特性，已被广泛研究作为治疗急性淋巴细胞白血病的生物制剂。L-ASNase 的需求主要通过从大肠杆菌和菊欧文氏菌生产重组 II 型 L-ASNase 来满足。然而，从原核生物来源的 L-ASNase 中存在免疫原性蛋白，已知会导致接受治疗的患者产生不良反应。因此，人们正在努力探索可以帮助减轻药物免疫原性的策略。本综述概述了酶工程技术和技术的最新生物技术突破，这些技术用于提高抗白血病 L-ASNase 的功效，同时考虑到 L-ASNase 的药理学重要性。
