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.com
Volume 9
Journal of Biotechnology & Biomaterials
ISSN: 2155-952X
JOINT EVENT
February 28-March 02, 2019 | Berlin, Germany
5
th
International Conference on
Enzymology and Protein Chemistry
&
22
nd
Global Congress on
Biotechnology
Biotechnology 2019
Enzymology 2019
February 28-March 02, 2019
&
Protein engineering applied to obtain biobetters of antitumor enzyme asparaginase
Gisele Monteiro, Costa I M, Costa-Silva T A, Effer B, Meira-Lima G, Biasoto H P, Silva C, Pessoa A
and
Rangel-Yagui C
University of São Paulo, Brazil
A
sparaginase (ASNase), an enzyme biotechnologically produced by bacteria, is one of the most important compounds
in polychemotherapy to treat acute lymphoblastic leukemia (ALL) in children. There are only three options available as
medicine: native enzyme from
Erwinia chrysanthemi
(ErA) or extracted from
Escherichia coli
(EcA) and formulated as native
or PEGylated (PEG-EcA). However, these options yet present some problems in patients, such as to elicit hypersensitivity and
allergenic reactions, neurotoxicity, and hyperammonemia. Aiming to avoid some of these problems, our research group has
developed several different mutant proteoforms, expressed in bacteria and yeast, in periplasmic or secreted to extracellular
space; with improvement in specific activity, kinetic parameters and stability; different oligomerization states, glycosylated or
not, through engineering of genes from
E. coli
,
E. chrysanthemi
and
S. cerevisiae
. We obtained mutants from
E. coli
ASNase
more resistant to human proteases and less immunogenic. In relation to E. chrysanthemi enzyme, our mutants present higher
asparaginase activity than the native form, with improved kcat. In addition, we obtained strains of Pichia pastoris that express
glycosylated ASNases from bacteria. Last but noteworthy, we obtained
P. pastoris
and
E. coli
strains that express active ASNases
from
S. cerevisiae
, an eukaryotic promising options to replace bacterial formulations.
Biography
Gisele Monteiro has completed her PhD at the University of São Paulo in Molecular Biology. Currently, she is an Associate Professor of Pharmaceutical Biotechnology
in the Faculty of Pharmaceutical Sciences (FCF/USP) and the Vice-Coordinator of the Graduate Course in Biochemical-Pharmaceutical Technology. She has published
more than 20 papers in reputed journals and has been serving as an Associate Editor of Brazilian Journal of Microbiology. She received 10 scientific awards, national and
international. Her main scientific interest is the study of antitumor drugs and the engineering of proteins used as biopharmaceuticals, such as asparaginase.
smgisele@usp.brGisele Monteiro et al., J Biotechnol Biomater 2019, Volume 9
DOI: 10.4172/2155-952X-C2-115