Metagenomic discovery and functional validation of L-asparaginases with anti-leukemic effect from the Caspian Sea

Metagenomic discovery and functional validation of L-asparaginases with anti-leukemic effect from the Caspian Sea

Summary: By screening 27,000 publicly available prokaryotic genomes, we recovered ca. 6300 type I and ca. 5200 type II putative L-asparaginase highlighting the vast potential of prokaryotes. Caspian water with similar salt composition to the human serum was targeted for in silico L-asparaginase scre...

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Main Authors: Motahareh Sobat, Sedigheh Asad, Mahboubeh Kabiri, Maliheh Mehrshad
Format: Article
Language:English
Published: Elsevier 2021-01-01
Series:iScience
Subjects:
Biological Sciences
Cell Biology
Cancer
In Silico Biology
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004220311706
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spelling doaj-6e687463de60469696c904d2f85106cb2021-01-24T04:28:57ZengElsevieriScience2589-00422021-01-01241101973Metagenomic discovery and functional validation of L-asparaginases with anti-leukemic effect from the Caspian SeaMotahareh Sobat0Sedigheh Asad1Mahboubeh Kabiri2Maliheh Mehrshad3Department of Biotechnology, College of Science, University of Tehran, Tehran, IranDepartment of Biotechnology, College of Science, University of Tehran, Tehran, Iran; Corresponding authorDepartment of Biotechnology, College of Science, University of Tehran, Tehran, IranDepartment of Ecology and Genetics, Limnology and Science for Life Laboratory, Uppsala University, Uppsala, SwedenSummary: By screening 27,000 publicly available prokaryotic genomes, we recovered ca. 6300 type I and ca. 5200 type II putative L-asparaginase highlighting the vast potential of prokaryotes. Caspian water with similar salt composition to the human serum was targeted for in silico L-asparaginase screening. We screened ca. three million predicted genes of its assembled metagenomes that resulted in annotation of 87 putative L-asparaginase genes. The L-asparagine hydrolysis was experimentally confirmed by synthesizing and cloning three selected genes in E. coli. Catalytic parameters of the purified enzymes were determined to be among the most desirable reported values. Two recombinant enzymes represented remarkable anti-proliferative activity (IC50 <1IU/ml) against leukemia cell line Jurkat while no cytotoxic effect on human erythrocytes or human umbilical vein endothelial cells was detected. Similar salinity and ionic concentration of the Caspian water to the human serum highlights the potential of secretory L-asparaginases recovered from these metagenomes as potential treatment agents.http://www.sciencedirect.com/science/article/pii/S2589004220311706Biological SciencesCell BiologyCancerIn Silico Biology
collection DOAJ
language English
format Article
sources DOAJ
author Motahareh Sobat
Sedigheh Asad
Mahboubeh Kabiri
Maliheh Mehrshad
spellingShingle Motahareh Sobat
Sedigheh Asad
Mahboubeh Kabiri
Maliheh Mehrshad
Metagenomic discovery and functional validation of L-asparaginases with anti-leukemic effect from the Caspian Sea
iScience
Biological Sciences
Cell Biology
Cancer
In Silico Biology
author_facet Motahareh Sobat
Sedigheh Asad
Mahboubeh Kabiri
Maliheh Mehrshad
author_sort Motahareh Sobat
title Metagenomic discovery and functional validation of L-asparaginases with anti-leukemic effect from the Caspian Sea
title_short Metagenomic discovery and functional validation of L-asparaginases with anti-leukemic effect from the Caspian Sea
title_full Metagenomic discovery and functional validation of L-asparaginases with anti-leukemic effect from the Caspian Sea
title_fullStr Metagenomic discovery and functional validation of L-asparaginases with anti-leukemic effect from the Caspian Sea
title_full_unstemmed Metagenomic discovery and functional validation of L-asparaginases with anti-leukemic effect from the Caspian Sea
title_sort metagenomic discovery and functional validation of l-asparaginases with anti-leukemic effect from the caspian sea
publisher Elsevier
series iScience
issn 2589-0042
publishDate 2021-01-01
description Summary: By screening 27,000 publicly available prokaryotic genomes, we recovered ca. 6300 type I and ca. 5200 type II putative L-asparaginase highlighting the vast potential of prokaryotes. Caspian water with similar salt composition to the human serum was targeted for in silico L-asparaginase screening. We screened ca. three million predicted genes of its assembled metagenomes that resulted in annotation of 87 putative L-asparaginase genes. The L-asparagine hydrolysis was experimentally confirmed by synthesizing and cloning three selected genes in E. coli. Catalytic parameters of the purified enzymes were determined to be among the most desirable reported values. Two recombinant enzymes represented remarkable anti-proliferative activity (IC50 <1IU/ml) against leukemia cell line Jurkat while no cytotoxic effect on human erythrocytes or human umbilical vein endothelial cells was detected. Similar salinity and ionic concentration of the Caspian water to the human serum highlights the potential of secretory L-asparaginases recovered from these metagenomes as potential treatment agents.
topic Biological Sciences
Cell Biology
Cancer
In Silico Biology
url http://www.sciencedirect.com/science/article/pii/S2589004220311706
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AT mahboubehkabiri metagenomicdiscoveryandfunctionalvalidationoflasparaginaseswithantileukemiceffectfromthecaspiansea
AT malihehmehrshad metagenomicdiscoveryandfunctionalvalidationoflasparaginaseswithantileukemiceffectfromthecaspiansea
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