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Int J Biol Macromol. 2021 Dec 15;196:151-162. doi: 10.1016/j.ijbiomac.2021.12.015. Epub 2021 Dec 15.

Microbial arginine deiminase: A multifaceted green catalyst in biomedical sciences.

International journal of biological macromolecules

Anubhuti Kawatra, Rakhi Dhankhar, Pooja Gulati

Affiliations

  1. Medical Microbiology and Bioprocess Technology Laboratory, Department of Microbiology, Maharshi Dayanand University, Rohtak, Haryana, India.
  2. Medical Microbiology and Bioprocess Technology Laboratory, Department of Microbiology, Maharshi Dayanand University, Rohtak, Haryana, India. Electronic address: [email protected].

PMID: 34920062 DOI: 10.1016/j.ijbiomac.2021.12.015

Abstract

Arginine deiminase is a well-recognized guanidino-modifying hydrolase that catalyzes the conversion of L-arginine to citrulline and ammonia. Their biopotential to regress tumors via amino acid deprivation therapy (AADT) has been well established. PEGylated formulation of recombinant Mycoplasma ADI is in the last-phase clinical trials against various arginine-auxotrophic cancers like hepatocellular carcinoma, melanoma, and mesothelioma. Recently, ADIs have attained immense importance in several other biomedical applications, namely treatment of Alzheimer's, as an antiviral drug, bioproduction of nutraceutical L-citrulline and bio-analytics involving L-arginine detection. Considering the wide applications of this biodrug, the demand for ADI is expected to escalate several-fold in the coming years. However, the sustainable production aspects of the enzyme with improved pharmacokinetics is still limited, creating bottlenecks for effective biopharmaceutical development. To circumvent the lacunae in enzyme production with appropriate paradigms of 'quality-by-design' an explicit overview of its properties with 'biobetter' formulations strategies are required. Present review provides an insight into all the potential biomedical applications of ADI along with the improvements required for its reach to clinics. Recent research advances with special emphasis on the development of ADI as a 'biobetter' enzyme have also been comprehensively elaborated.

Copyright © 2021 Elsevier B.V. All rights reserved.

Keywords: Antiviral; Applications; Arginine deiminase (ADI); Biomedical sciences; Cancer; Improvement strategies

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