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Biomedical applications of microbial phenylalanine ammonia lyase: Current status and future prospects.
Biochimie ( IF 3.3 ) Pub Date : 2020-08-21 , DOI: 10.1016/j.biochi.2020.08.009
Anubhuti Kawatra 1 , Rakhi Dhankhar 1 , Aparajita Mohanty 2 , Pooja Gulati 1
Affiliation  

Phenylalanine ammonia lyase (PAL) has recently emerged as an important therapeutic enzyme with several biomedical applications. The enzyme catabolizes l-phenylalanine to trans-cinnamate and ammonia. PAL is widely distributed in higher plants, some algae, ferns, and microorganisms, but absent in animals. Although microbial PAL has been extensively exploited in the past for producing industrially important metabolites, its high substrate specificity and catalytic efficacy lately spurred interest in its biomedical applications. PEG-PAL drug named Palynziq™, isolated from Anabaena variabilis has been recently approved for the treatment of adult phenylketonuria (PKU) patients. Further, it has exhibited high potency in regressing tumors and treating tyrosine related metabolic abnormalities like tyrosinemia. Several therapeutically valuable metabolites have been biosynthesized via its catalytic action including dietary supplements, antimicrobial peptides, aspartame, amino-acids, and their derivatives. This review focuses on all the prospective biomedical applications of PAL. It also provides an overview of the structure, production parameters, and various strategies to improve the therapeutic potential of this enzyme. Engineered PAL with improved pharmacodynamic and pharmacokinetic properties will further establish this enzyme as a highly efficient biological drug.



中文翻译:

微生物苯丙氨酸氨裂合酶的生物医学应用:现状和未来前景。

苯丙氨酸氨裂合酶(PAL)最近已成为一种重要的治疗酶,在多种生物医学应用中均得到应用。酶分解代谢-苯丙氨酸,以反式-肉桂酸酯和氨。PAL广泛分布于高等植物,一些藻类,蕨类和微生物中,但在动物中却不存在。尽管微生物PAL在过去已经被广泛地用于生产工业上重要的代谢产物,但是其高的底物特异性和催化功效近来引起了对其生物医学应用的兴趣。PEG-PAL药物Palynziq™,从鱼腥藻中分离最近已批准用于治疗成人苯丙酮尿症(PKU)的患者。此外,它在消退肿瘤和治疗酪氨酸相关的代谢异常如酪氨酸血症方面显示出很高的效力。已经通过其催化作用生物合成了几种具有治疗价值的代谢物,包括膳食补充剂,抗菌肽,阿斯巴甜,氨基酸及其衍生物。这篇综述着重于PAL的所有前瞻性生物医学应用。它还概述了结构,生产参数和各种提高该酶治疗潜力的策略。具有改善的药代动力学和药代动力学特性的工程PAL将进一步确立这种酶作为高效生物药物的地位。

更新日期:2020-09-01
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