Bio‐based production of organic acids with Corynebacterium glutamicum

Abstract

The shortage of oil resources, the steadily rising oil prices and the impact of its use on the environment evokes an increasing political, industrial and technical interest for development of safe and efficient processes for the production of chemicals from renewable biomass. Thus, microbial fermentation of renewable feedstocks found its way in white biotechnology, complementing more and more traditional crude oil-based chemical processes. Rational strain design of appropriate microorganisms has become possible due to steadily increasing knowledge on metabolism and pathway regulation of industrially relevant organisms and, aside from process engineering and optimization, has an outstanding impact on improving the performance of such hosts. Corynebacterium glutamicum is well known as workhorse for the industrial production of numerous amino acids. However, recent studies also explored the usefulness of this organism for the production of several organic acids and great efforts have been made for improvement of the performance. This review summarizes the current knowledge and recent achievements on metabolic engineering approaches to tailor C. glutamicum for the bio-based production of organic acids. We focus here on the fermentative production of pyruvate, l-and d-lactate, 2-ketoisovalerate, 2-ketoglutarate, and succinate. These organic acids represent a class of compounds with manifold application ranges, e.g. in pharmaceutical and cosmetics industry, as food additives, and economically very interesting, as precursors for a variety of bulk chemicals and commercially important polymers.Funding Information Work in the laboratories of the authors was supported by the Fachagentur Nachwachsende Rohstoffe (FNR) of the Bundesministerium für Ernährung, Landwirtschaft und Verbraucherschutz (BMELV; FNR Grants 220-095-08A and 220-095-08D; Bio-ProChemBB project, ERA-IB programme), by the Deutsche Bundesstiftung Umwelt (DBU Grant AZ13040/05) and the Evonik Degussa AG.

Enhanced acetic acid and succinic acid production under microaerobic conditions by Corynebacterium glutamicum harboring Escherichia coli transhydrogenase gene pntAB

“…Succinic acid is an important compound as a building block of useful chemicals (Cheng et al, 2012;Delhomme et al, 2009). Many studies on metabolic engineering of microorganisms for succinic acid production have been reported ( Okino et al, 2008;Thakker et al, 2012;Wang et al, 2011a, b;Wendisch et al, 2006;Wieschalka et al, 2013;Yuzbashev et al, 2010;Zhang et al, 2009Zhang et al, , 2010. From the viewpoint of metabolic engineering of C. glutamicum for succinic acid production, introduction of E. coli pntAB seems to be an effective way to enhance succinic acid production under microaerobic conditions.…”

“…Nowadays, it is commonly used to produce useful buildingblock chemicals, such as lactic acid and succinic acid (Wendisch et al, 2006;Wieschalka et al, 2013). C. glutamicum is used in microbial bioproduction systems to produce various amino acids, such as lysine, valine, and glutamic acid.…”

Carbon Flux Analysis by 13 C Nuclear Magnetic Resonance To Determine the Effect of CO 2 on Anaerobic Succinate Production by Corynebacterium glutamicum

“…The total amounts of internal and external organic acids were fitted to exponential curves, which were used to calculate the n value, the number of protons exported concomitantly with each molecule of organic acid, numerically, as described by Carvalho et al (21). The intracellular pH was determined by 31 P NMR, and the relative concentrations of the ionized forms were obtained using a pK a1 value of 4.2 and a pK a2 value of 5.6 for succinic acid.…”

“…4) shows intense resonances due to extracellular succinate (␦, 33.4 ppm) and lactate (␦, 20.6 ppm). More importantly, two small resonances appear at 33.7 ppm and 20.7 ppm, which arise from these organic acids inside the cell (internal pH, approximately 6.3, as determined by 31 P NMR [data not shown]). The kinetics of glucose consumption and the buildup of intra-and extracellular pools under anaerobic conditions (with and without CO 2 ) are shown in Fig.…”

Transcription of Sialic Acid Catabolism Genes in Corynebacterium glutamicum Is Subject to Catabolite Repression and Control by the Transcriptional Repressor NanR

“…he Gram-positive Corynebacterium glutamicum is mostly known for its application in the industrial production of amino acids, mainly L-glutamate and L-lysine (1,2), and has become a versatile cell factory for the production of various commodity products (3)(4)(5). C. glutamicum utilizes a large variety of sugars and organic acids as sources of carbon and energy (6,7) and additionally has been genetically engineered for the utilization of alternative feedstocks such as starch, glycerol, xylose, glucuronic acid, and N-acetylglucosamine (8)(9)(10)(11)(12).…”