Identification of L-asparaginases from Streptomyces strains with competitive activity and immunogenic profiles: a bioinformatic approach

PeerJ. 2020 Nov 13:8:e10276. doi: 10.7717/peerj.10276. eCollection 2020.

Abstract

The enzyme L-asparaginase from Escherichia coli is a therapeutic enzyme that has been a cornerstone in the clinical treatment of acute lymphoblastic leukemia for the last decades. However, treatment effectiveness is limited by the highly immunogenic nature of the protein and its cross-reactivity towards L-glutamine. In this work, a bioinformatic approach was used to identify, select and computationally characterize L-asparaginases from Streptomyces through sequence-based screening analyses, immunoinformatics, homology modeling, and molecular docking studies. Based on its predicted low immunogenicity and excellent enzymatic activity, we selected a previously uncharacterized L-asparaginase from Streptomyces scabrisporus. Furthermore, two putative asparaginase binding sites were identified and a 3D model is proposed. These promising features allow us to propose L-asparaginase from S. scabrisporus as an alternative for the treatment of acute lymphocytic leukemia.

Keywords: Acute lymphocytic leukemia; Bioinformatics; L-asparaginase; Streptomyces.

Grants and funding

This work was supported by PAPIIT-DGAPA UNAM grant IN210618 (Alejandro Huerta-Saquero) and grant IN209620 (Ernesto Perez-Rueda); and Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo (P918PTE0261) (Ernesto Perez-Rueda). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.