title: Human recombinant lysosomal enzymes produced in microorganisms.
abstract: 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.
authors.affiliation: Institute for the Study of Inborn Errors of Metabolism, School of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Ángela J
authors.initials: ÁJ
authors.lastname: Espejo-Mojica
authors.affiliation: Institute for the Study of Inborn Errors of Metabolism, School of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia. Electronic address: cjalmeciga@javeriana.edu.co.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Alméciga-Díaz
authors.affiliation: Institute for the Study of Inborn Errors of Metabolism, School of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia; Chemical Department, School of Science, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rodríguez
authors.affiliation: Institute for the Study of Inborn Errors of Metabolism, School of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Ángela
authors.initials: Á
authors.lastname: Mosquera
authors.affiliation: Institute for the Study of Inborn Errors of Metabolism, School of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Dennis
authors.initials: D
authors.lastname: Díaz
authors.affiliation: Institute for the Study of Inborn Errors of Metabolism, School of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Laura
authors.initials: L
authors.lastname: Beltrán
authors.affiliation: Institute for the Study of Inborn Errors of Metabolism, School of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Sergio
authors.initials: S
authors.lastname: Díaz
authors.affiliation: Institute for the Study of Inborn Errors of Metabolism, School of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Pimentel
authors.affiliation: Institute for the Study of Inborn Errors of Metabolism, School of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Jefferson
authors.initials: J
authors.lastname: Moreno
authors.affiliation: Institute for the Study of Inborn Errors of Metabolism, School of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Jhonnathan
authors.initials: J
authors.lastname: Sánchez
authors.affiliation: School of Chemical Engineering, Purdue University, West Lafayette, IN, USA.
authors.forename: Oscar F
authors.initials: OF
authors.lastname: Sánchez
authors.affiliation: Chemical Department, School of Science, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Henry
authors.initials: H
authors.lastname: Córdoba
authors.affiliation: Laboratorio de Biotecnología Molecular, Grupo de Biotecnología Ambiental e Industrial (GBAI), School of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Raúl A
authors.initials: RA
authors.lastname: Poutou-Piñales
authors.affiliation: Institute for the Study of Inborn Errors of Metabolism, School of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Barrera
mesh_terms: D000818:Animals; D004926:Escherichia coli / Q000378:metabolism; D005822:Genetic Vectors / Q000378:metabolism; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000188:drug therapy*; D008247:Lysosomes / Q000201:enzymology*; D010944:Plants / Q000235:genetics; D011506:Proteins / Q000302:isolation & purification* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000627:therapeutic use; D004718:Saccharomycetales / Q000378:metabolism
chemical_list: D011506:Proteins; D011994:Recombinant Proteins; C018589:lysosomal proteins
keywords: Escherichia coli; Glycosylation; Lysosomal storage disease; Lysosome; Recombinant protein; Yeast