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Microbial enzymes for deprivation of amino acid metabolism in malignant cells: biological strategy for cancer treatment

Abstract

Amino acid deprivation therapy (AADT) is emerging as a promising strategy for the development of novel therapeutics against cancer. This biological therapy relies upon the differences in the metabolism of cancer and normal cells. The rapid growth of tumors results in decreased expression of certain enzymes leading to auxotrophy for some specific amino acids. These auxotrophic tumors are targeted by amino acid–depleting enzymes. The depletion of amino acid selectively inhibits tumor growth as the normal cells can synthesize amino acids by their usual machinery. The enzymes used in AADT are mostly obtained from microbes for their easy availability. Microbial l-asparaginase is already approved by FDA for the treatment of acute lymphoblastic leukemia. Arginine deiminase and methionase are under clinical trials and the therapeutic potential of lysine oxidase, glutaminase and phenylalanine ammonia lyase is also being explored. The present review provides an overview of microbial amino acid depriving enzymes. Various attributes of these enzymes like structure, mode of action, production, formulations, and targeted cancers are discussed. The challenges faced and the combat strategies to establish AADT in standard cancer armamentarium are also reviewed.

Key Points

• Amino acid deprivation therapy is a potential therapy for auxotrophic tumors.

• Microbial enzymes are used due to their ease of manipulation and high productivity.

• Enzyme properties are improved by PEGylation, encapsulation, and genetic engineering.

• AADT can be employed as combinational therapy for better containment of cancer.

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Acknowledgments

RD is grateful to the Department of Science and Technology-Science and Engineering Research Board (DST-SERB) and MDU, Rohtak, for providing the fellowship. The authors thank DST for providing FIST grant (1196 SR/FST/LS-I/2017/4) for the development of infrastructural facilities.

Funding

This study was financially supported by DST-SERB (SB/YS/LS-145/2014).

Author information

PG conceived and designed the layout of the manuscript. RD and PG carried out the literature survey. RD and VG wrote the manuscript. SK and RKK prepared the figures. PG critically analyzed and revised the manuscript. All authors read and approved the manuscript.

Correspondence to Pooja Gulati.

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Dhankhar, R., Gupta, V., Kumar, S. et al. Microbial enzymes for deprivation of amino acid metabolism in malignant cells: biological strategy for cancer treatment. Appl Microbiol Biotechnol (2020). https://doi.org/10.1007/s00253-020-10432-2

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Keywords

  • Anti-cancerous enzymes
  • Anti-tumor enzymes
  • Amino acid deprivation therapy
  • Auxotrophic tumors
  • Biological cancer treatment
  • PEGylation