酶工程策略在L-Asparaginase作为生物制剂中的生物增强中的应用
Enzyme Engineering Strategies for the Bioenhancement of L-Asparaginase Used as a Biopharmaceutical.
发表日期:2023 Sep 12
作者:
Javiera Miranda, Nicolás Lefin, Jorge F Beltran, Lisandra Herrera Belén, Argyro Tsipa, Jorge G Farias, Mauricio Zamorano
来源:
BIODRUGS
摘要:
近年来,由于微生物重组酶具有高效、选择性和生物相容性的催化特性,工业生产中的重组酶产量急剧增加。L-天门冬酰胺酶(L-ASNase)是一种属于酰胺水解酶类的酶,能催化将L-天门冬氨酸水解为L-天冬氨酸和氨。广泛研究表明,L-ASNase因其抗肿瘤特性而作为生物制剂被广泛用于急性淋巴细胞性白血病的治疗。L-ASNase的需求主要通过大肠杆菌和菊花病菌产生的重组II型L-ASNase来满足。然而,源自原核生物的L-ASNase中存在免疫原蛋白已知会导致接受治疗的患者出现不良反应。因此,人们正在努力探索可以减轻药物免疫原性的策略。本综述概述了近期酶工程技术和技术在改进抗白血病L-ASNase方面的生物技术突破,同时考虑到L-ASNase的药理重要性。© 2023 Springer Nature Switzerland AG,作者独家授权。
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.© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.