Metabolic Engineering of Corynebacterium Glutamicum Aimed at Alternative Carbon Sources and New Products

Abstract

Corynebacterium glutamicum is well known as the amino acid-producing workhorse of fermentation industry, being used for multi-million-ton scale production of glutamate and lysine for more than 60 years. However, it is only recently that extensive research has focused on engineering it beyond the scope of amino acids. Meanwhile, a variety of corynebacterial strains allows access to alternative carbon sources and/or allows production of a wide range of industrially relevant compounds. Some of these efforts set new standards in terms of titers and productivities achieved whereas others represent a proof-of-principle. These achievements manifest the position of C. glutamicum as an important industrial microorganism with capabilities far beyond the traditional amino acid production. In this review we focus on the state of the art of metabolic engineering of C. glutamicum for utilization of alternative carbon sources, (e.g. coming from wastes and unprocessed sources), and construction of C. glutamicum strains for production of new products such as diamines, organic acids and alcohols

Metabolic Engineering of an ATP-Neutral Embden-Meyerhof-Parnas Pathway in Corynebacterium glutamicum: Growth Restoration by an Adaptive Point Mutation in NADH Dehydrogenase

“…In C. glutamicum, glucose, fructose, and sucrose are imported and phosphorylated by the phosphoenolpyruvate-dependent carbohydrate:phosphotransferase system (PTS) and enter the EMP pathway as glucose-6-phosphate or fructose 1,6-bisphosphate (25,26). As is typical, the EMP pathway yields 2 mol of ATP per mol of glucose in C. glutamicum.…”

Metabolic Engineering of Corynebacterium glutamicum for Methanol Metabolism

“…In addition, extensive research has focused on engineering C. glutamicum for the microbial production of a variety of other commercially interesting compounds (1), such as organic acids (2)(3)(4), diamines (5-7), and alcohols (8)(9)(10). The natural substrate spectrum of C. glutamicum includes sugars, organic acids, and alcohols, but for industrial production processes mainly glucose (from starch) or sucrose and fructose (from molasses) are used as carbon sources (11)(12)(13). The availability and price of sugars are influenced by seasonal variations and weather conditions and are also subject to price regulations and import limitations imposed on agricultural products.…”

Amino acids production focusing on fermentation technologies – A review

“…C. glutamicum is used for the production of several amino acids such as L-glutamate, Llysine, L-phenylalanine (Hermann, 2003), L-threonine (Kumagai, 2000), L-tryptophan (Leuchtenberger et al, 2005), L-serine, L-proline, L-glutamine, L-arginine (Utagawa, 2004) and L-isoleucine. It prefers glucose as carbon source (Eggeling and Bott, 2005), but it can utilize also other sugars such as sucrose, fructose, ribose, mannose and maltose (Zahoor et al, 2012). Its optimal growth conditions are at a temperature of 30°C and a pH of 7 (Liebl, 2005).…”

“…Moreover metabolic engineering tools enable the development of more environmentally sustainable technologies (Zahoor et al, 2012;Rittmann et al, 2008). Indeed, the construction of a recombinant strain allows not only to use a larger range of carbon sources including galactose, lactose, xylose or arabinose, but also alternative feedstocks, such as glycerol, which can be found in industrial by products, and thereby do not compete with food or energy production (Ikeda and Takeno, 2013).…”