Microbial Cell Factories (Feb 2024)

The recombinant l-lysine α-oxidase from the fungus Trichoderma harzianum promotes apoptosis and necrosis of leukemia CD34 + hematopoietic cells

  • Mariana do Nascimento Costa,
  • Thiago Aparecido Silva,
  • Dimitrius Santiago Passos Simões Fróes Guimarães,
  • Rafael Ricci-Azevedo,
  • Felipe Roberti Teixeira,
  • Leonardo Reis Silveira,
  • Marcelo Damário Gomes,
  • Vítor Marcel Faça,
  • Eduardo Brandt de Oliveira,
  • Rodrigo T. Calado,
  • Roberto N. Silva

DOI
https://doi.org/10.1186/s12934-024-02315-2
Journal volume & issue
Vol. 23, no. 1
pp. 1 – 16

Abstract

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Abstract Background In hematologic cancers, including leukemia, cells depend on amino acids for rapid growth. Anti-metabolites that prevent their synthesis or promote their degradation are considered potential cancer treatment agents. Amino acid deprivation triggers proliferation inhibition, autophagy, and programmed cell death. l-lysine, an essential amino acid, is required for tumor growth and has been investigated for its potential as a target for cancer treatment. l-lysine α-oxidase, a flavoenzyme that degrades l-lysine, has been studied for its ability to induce apoptosis and prevent cancer cell proliferation. In this study, we describe the use of l-lysine α-oxidase (LO) from the filamentous fungus Trichoderma harzianum for cancer treatment. Results The study identified and characterized a novel LO from T. harzianum and demonstrated that the recombinant protein (rLO) has potent and selective cytotoxic effects on leukemic cells by triggering the apoptotic cascade through mitochondrial dysfunction. Conclusions The results support future translational studies using the recombinant LO as a potential drug for the treatment of leukemia.

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