Still, yeast glycosylation differs from human N- and O- glycosylation, and to circumvent this limitation a major effort was directed toward yeast glycoengineering. coli possess native PTM machinery and lack endotoxins ( Demain and Vaishnav, 2009 MartÃnez et al., 2012). cerevisiae, Pichia pastoris, Yarrowia lipolytica, Hansenula polymorpha), which are robust, easy to genetically manipulate, cost-effective, and unlike E. One of the preferred heterologous expression systems are generally recognized as safe (GRAS) yeasts (e.g. Microbe expression system-derived recombinant proteins, on the other hand, face several limitations, such as post-translational modifications (PTMs), potential immunogenicity, poor stability and short serum half-life. Over the past decades, the constantly broadening biopharmaceutical industry exhibited the blossom of vaccines, therapeutic monoclonal antibodies (mAbs), recombinant enzymes, cytokines and blood-related proteins, most of which are produced in mammalian cells (predominantly Chinese hamster ovary cells, CHO) ( Walsh, 2010, 2018), a time-consuming, laborious and expensive process. Currently, apart from gonadotropic hormones, which are produced only in mammalian cells given their specific glycosylation ( Orvieto and Seifer, 2016), most of the other commercialized hormones are synthesized by recombinant Saccharomyces cerevisiae (insulin, glucagon, GH) or E.coli. coli-produced growth hormone (GH) in 1985 ( Wang et al., 2017). One of the pioneering examples is Escherichia coli-produced insulin, which was Food and Drug Administration (FDA)-approved and commercialized in 1982, followed by the E. The development of genetic engineering tools and genome sequencing enabled the emergence of heterologous production as an alternative supply strategy. ![]() Biopharmaceuticals and medicinal natural products (NPs) embrace a vast and continuously expanding range of applications in human medicine, which requires high-scale production to meet clinical demands and prevent natural source-related restraints.
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