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The sweet branch of metabolic engineering: cherry-picking the low-hanging sugary fruits

机译：代谢工程的甜头：挑摘低悬垂的含糖水果

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In the first science review on the then nascent Metabolic Engineering field in 1991, Dr. James E. Bailey described how improving erythropoietin (EPO) glycosylation can be achieved via metabolic engineering of Chinese hamster ovary (CHO) cells. In the intervening decades, metabolic engineering has brought sweet successes in glycoprotein engineering, including antibodies, vaccines, and other human therapeutics. Today, not only eukaryotes (CHO, plant, insect, yeast) are being used for manufacturing protein therapeutics with human-like glycosylation, newly elucidated bacterial glycosylation systems are enthusiastically embraced as potential breakthrough to revolutionize the biopharmaceutical industry. Notwithstanding these excitement in glycoprotein, the sweet metabolic engineering reaches far beyond glycoproteins. Many different types of oligo- and poly-saccharides are synthesized with metabolically engineered cells. For example, several recombinant hyaluronan bioprocesses are now in commercial production, and the titer of 2′-fucosyllactose, the most abundant fucosylated trisaccharide in human milk, reaches over 20 g/L with engineered E. coli cells. These successes represent only the first low hanging fruits, which have been appreciated scientifically, medically and fortunately, commercially as well. As one of the four building blocks of life, sugar molecules permeate almost all aspects of life. They are also unique in being intimately associated with all major types of biopolymers (including DNA/RNA, proteins, lipids) meanwhile they stand alone as bioactive polysaccharides, or free soluble oligosaccharides. As such, all sugar moieties in biological components, small or big and free or bound, are important targets for metabolic engineering. Opportunities abound at the interface of glycosciences and metabolic engineering. Continued investment and successes in this branch of metabolic engineering will make vastly diverse sugar-containing molecules (a.k.a. glycoconjugates) available for biomedical applications, sustainable technology development, and as invaluable tools for basic scientific research. This short review focuses on the most recent development in the field, with emphasis on the synthesis technology for glycoprotein, polysaccharide, and oligosaccharide.
机译：在1991年当时新生的代谢工程领域的第一篇科学综述中，James E. Bailey博士描述了如何通过中国仓鼠卵巢（CHO）细胞的代谢工程来改善促红细胞生成素（EPO）糖基化。在过去的几十年中，代谢工程在糖蛋白工程（包括抗体，疫苗和其他人类疗法）中取得了可喜的成就。如今，不仅真核生物（CHO，植物，昆虫，酵母菌）被用于生产具有人类样糖基化作用的蛋白质治疗剂，而且新近阐明的细菌糖基化系统也受到热烈欢迎，有望成为革新生物制药行业的潜在突破。尽管糖蛋白具有这些兴奋性，但是甜的代谢工程远远超出了糖蛋白。代谢工程化的细胞可合成许多不同类型的寡糖和多糖。例如，几种重组乙酰透明质酸生物工艺现已投入商业生产，工程化大肠杆菌细胞中人乳中最丰富的岩藻糖基化三糖2'-岩藻糖半乳糖的效价达到20 g / L以上。这些成功只是第一批低垂的果实，科学，医学和幸运的是，它们在商业上也受到赞赏。作为生命的四个基本组成部分之一，糖分子几乎渗透到生活的各个方面。它们在与所有主要类型的生物聚合物（包括DNA / RNA，蛋白质，脂质）密切相关方面也独树一帜，同时它们可单独作为生物活性多糖或游离可溶性寡糖使用。因此，生物组分中的所有糖部分，无论大小，游离或结合，都是代谢工程的重要目标。糖科学和代谢工程学之间的机会比比皆是。在新陈代谢工程这一领域的持续投资和成功将使种类繁多的含糖分子（也称为糖缀合物）可用于生物医学应用，可持续技术发展以及作为基础科学研究的宝贵工具。这篇简短的评论着重于该领域的最新发展，重点是糖蛋白，多糖和低聚糖的合成技术。

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