Cell-based and cell-free biocatalysis for the production of d -glucaric acid
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Biotechnology for Biofuels Open Access
REVIEW
Cell‑based and cell‑free biocatalysis for the production of d‑glucaric acid Lu‑Zhou Chen1, Si‑Ling Huang2, Jin Hou3, Xue‑Ping Guo2, Feng‑Shan Wang1,4 and Ju‑Zheng Sheng1,4*
Abstract d-Glucaric acid (GA) is a value-added chemical produced from biomass, and has potential applications as a versa‑ tile platform chemical, food additive, metal sequestering agent, and therapeutic agent. Marketed GA is currently produced chemically, but increasing demand is driving the search for eco-friendlier and more efficient production approaches. Cell-based production of GA represents an alternative strategy for GA production. A series of synthetic pathways for GA have been ported into Escherichia coli, Saccharomyces cerevisiae and Pichia pastoris, respectively, and these engineered cells show the ability to synthesize GA de novo. Optimization of the GA metabolic pathways in host cells has leapt forward, and the titer and yield have increased rapidly. Meanwhile, cell-free multi-enzyme catalysis, in which the desired pathway is constructed in vitro from enzymes and cofactors involved in GA biosynthesis, has also realized efficient GA bioconversion. This review presents an overview of studies of the development of cell-based GA production, followed by a brief discussion of potential applications of biosensors that respond to GA in these biosyn‑ thesis routes. Keywords: d-Glucaric acid, Escherichia coli, Yeast, Metabolic engineering, Cell-free synthetic biology, Biosensor Background d-Glucaric acid (GA), also called glucarate or saccharic acid, is a naturally occurring aldaric acid in animals and several types of fruits and vegetables [1, 2]. This compound has been used in many fields, including the chemical, food, pharmaceutical, and therapeutic industries [3]. From 2004, GA was classified as a “top value-added chemical from biomass” by the United States Department of Energy because of its potential applications as a material for making biodegradable detergents and biodegradable polymers such as nylons and plastics [4]. As it combines well with metal ions, it is also used as an imaging agent in tumor observation, a surfactant in sewage treatment, and a decolorizer in the treatment of synthetic dyes [5–7]. In medicine, GA is used to reduce cholesterol *Correspondence: [email protected] 1 Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China Full list of author information is available at the end of the article
and suppress tumor development [1]. GA could also enhance human immunity and reduce cancer risks if used as a food additive [8]. GA is a by-product of the glucuronic acid metabolism pathway (Fig. 1) in animal and plant cells [9]. This quantitatively minor route of glucose metabolism catalyzes the conversion of glucose to glucuronic acid (GlcA), ascorbic acid, and pentoses, and also provides biosynthetic precursors (nucleotide sugars) to synthesiz
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