TY - JOUR
T1 - Human recombinant lysosomal enzymes produced in microorganisms
AU - Espejo-Mojica, Ángela J.
AU - Alméciga-Díaz, Carlos J.
AU - Rodríguez, Alexander
AU - Mosquera, Ángela
AU - Díaz, Dennis
AU - Beltrán, Laura
AU - Díaz, Sergio
AU - Pimentel, Natalia
AU - Moreno, Jefferson
AU - Sánchez, Jhonnathan
AU - Sánchez, Oscar F.
AU - Córdoba, Henry
AU - Poutou-Piñales, Raúl A.
AU - Barrera, Luis A.
N1 - Publisher Copyright:
© 2015 Elsevier Inc..
PY - 2015/9/1
Y1 - 2015/9/1
N2 - Lysosomal storage diseases (LSDs) are caused by accumulation of partially degraded substrates within the lysosome, as a result of a function loss of a lysosomal protein. Recombinant lysosomal proteins are usually produced in mammalian cells, based on their capacity to carry out post-translational modifications similar to those observed in human native proteins. However, during the last years, a growing number of studies have shown the possibility to produce active forms of lysosomal proteins in other expression systems, such as plants and microorganisms. In this paper, we review the production and characterization of human lysosomal proteins, deficient in several LSDs, which have been produced in microorganisms. For this purpose, Escherichia coli, Saccharomyces cerevisiae, Pichia pastoris, Yarrowia lipolytica, and Ogataea minuta have been used as expression systems. The recombinant lysosomal proteins expressed in these hosts have shown similar substrate specificities, and temperature and pH stability profiles to those produced in mammalian cells. In addition, pre-clinical results have shown that recombinant lysosomal enzymes produced in microorganisms can be taken-up by cells and reduce the substrate accumulated within the lysosome. Recently, metabolic engineering in yeasts has allowed the production of lysosomal enzymes with tailored N-glycosylations, while progresses in E. coli N-glycosylations offer a potential platform to improve the production of these recombinant lysosomal enzymes. In summary, microorganisms represent convenient platform for the production of recombinant lysosomal proteins for biochemical and physicochemical characterization, as well as for the development of ERT for LSD.
AB - Lysosomal storage diseases (LSDs) are caused by accumulation of partially degraded substrates within the lysosome, as a result of a function loss of a lysosomal protein. Recombinant lysosomal proteins are usually produced in mammalian cells, based on their capacity to carry out post-translational modifications similar to those observed in human native proteins. However, during the last years, a growing number of studies have shown the possibility to produce active forms of lysosomal proteins in other expression systems, such as plants and microorganisms. In this paper, we review the production and characterization of human lysosomal proteins, deficient in several LSDs, which have been produced in microorganisms. For this purpose, Escherichia coli, Saccharomyces cerevisiae, Pichia pastoris, Yarrowia lipolytica, and Ogataea minuta have been used as expression systems. The recombinant lysosomal proteins expressed in these hosts have shown similar substrate specificities, and temperature and pH stability profiles to those produced in mammalian cells. In addition, pre-clinical results have shown that recombinant lysosomal enzymes produced in microorganisms can be taken-up by cells and reduce the substrate accumulated within the lysosome. Recently, metabolic engineering in yeasts has allowed the production of lysosomal enzymes with tailored N-glycosylations, while progresses in E. coli N-glycosylations offer a potential platform to improve the production of these recombinant lysosomal enzymes. In summary, microorganisms represent convenient platform for the production of recombinant lysosomal proteins for biochemical and physicochemical characterization, as well as for the development of ERT for LSD.
KW - Escherichia coli
KW - Glycosylation
KW - Lysosomal storage disease
KW - Lysosome
KW - Recombinant protein
KW - Yeast
UR - http://www.scopus.com/inward/record.url?scp=84940900300&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2015.06.001
DO - 10.1016/j.ymgme.2015.06.001
M3 - Review article
C2 - 26071627
AN - SCOPUS:84940900300
SN - 1096-7192
VL - 116
SP - 13
EP - 23
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 1-2
ER -