Corynebacterium biosynthesis

Muhammed, A. Studies on biosynthesis of polymetaphosphate by an enzyme from Corynebacterium xerosis. Biochim. Biophys. Acta, 54, 121-132 (1961)... 

Eikmanns, B.J., Eggeling, L., and Sahm, H. (1993). Molecular aspects of lysine, threonine, and isoleucine biosynthesis in Corynebacterium glutamicumP Antonie VanLeeuwen-hoek, 64(2), 145-163. 

Fig. 5. Carbon transitions in the split pathway of lysine biosynthesis in Corynebacterium glutamicum. Not all the reaction steps or all the metabolites are shown. A1 A2, A3, and A4 refer to the carbon atoms C1-C4 of aspartate and Pl5 P2, and P3 refer to Cl-C3 of pyruvate...

In the early years, L-Phe was microbially produced with Corynebacterium gluta-micum and E. coli strains which had been deregulated with respect to the end product via classical strain improvement. More recently, metabolic engineering has been employed to address nearly all aspects of the biosynthesis of L-Phe the work has been reviewed [70, 93]. 

The pathway of biosynthesis of L-lysine and L-threonine in Corynebacterium glutamicum is shown in Fig. 1. The first step, the formation of phosphoaspartate from aspartate, is catalyzed by aspertokinase and this enzyme is susceptible to the concerted feedback inhibition by L-lysine and L-threonine. The auxotrophic mutant of homoserine (or threonine plus methionine), lacking homoserine dehydrogenase, was constructed and found to produce L-lysine in the culture medium. Second, the mutants which show the threonine or methionine sensitive phenotype caused by the mutation on homoserine dehydrogenase (low activity) was also found to produce appreciable amounts of L-lysine in the culture medium. Furthermore, a lysine analogue (S-aminoethylcysteine) resistant mutant was obtained as an L-lysine producer and in this strain aspartokinase was insensitive to the feedback inhibition. 

Figure 6.1 Carbon core metabolism of Corynebacterium glutamicum comprising the major catabolic routes of pentose phosphate pathway and Embden-Meyerhof-Parnas pathway, tricarboxylic acid cycle, glyoxylate shunt, and anaplerotic reactions. The relevance of the individual pathways and carbon building blocks for biosynthesis of the broad product...

A novel type of N-acetylglutamate synthase is involved in the first step of arginine biosynthesis in Corynebacterium glutamicum. BMC Genomics,... 

Y, and Woo, H.M. (2014) Biosynthesis of pinene from glucose using metabolically-engineered Corynebacterium glutamicum. Biotechnol. Lett, 36 (10), 2069-2077. 

Corynebacterium actively excretes amino acids through its cell wall membrane and does not degrade L-lysine due to the lack of lysine-decarboxylase. For 60 years all these characteristics have made this microbe the species of choice in L-lysine production. In addition it demonstrates the potential of natural biosynthesis pathways for commercial purposes. In contrast Escherichia coli entered the field of industrial amino acid fermentation not because of comparable advantages provided by nature but because of the availability of effective tools for genetic engineering. In the early 1980s such methods were state of the art for Escherichia coli but were only on an infant level for Corynebacterium. Developing industrial strains based on Escherichia coli, which at that time was not broadly covered by intellectual property (IP), provided room to build new IP in the field of amino acid fermentation. 

Methionine biosynthesis is controlled by the metabolic regulation of enzymes in the pathway. Species of Corynebacterium and Brevibacterium have much simpler regulatory mechanisms than E. coli for methionine biosynthesis and are the preferred microbes for overproduction. Aspartokinase is a major enzyme that catalyzes the phosphorylation of aspartic acid and redirects the flux to aspartate family of amino acids. 

In E. coli there are three aspartokinases I (coded by thrA), II (coded by met L), and III (coded by lysC) and two homoserine dehydrogenases I and II that are inhibited or repressed by only one or two amino acids of the aspartate family which ensures that pathway is not shut down with the excess of one product. Each amino acid regulates the first enzyme in its branch to maintain the proper ratio of the amino acids. In Corynebacterium, the regulation is much simpler with only one aspartokinase and here the amino acid biosynthesis is controlled by the synergistic action of the end products. 

Gande R, Gibson KJC, Brown AK, Krumbach K, Dover LG, Sahm H, et al. Acyl-CoA carboxylases accD2 and accD3), together with a unique polyketide synthase (Cg-pks), are key to mycohc acid biosynthesis in Corynebacteriaceae such as Corynebacterium glutamicum and Mycobacterium tuberculosis.J Biol Chem 2004 279 44847-57. 

Hwang BJ, Yeom HJ, Kim Y, Lee HS. Corynebacterium glutamicum utilizes both transsuMuration and direct sulfhydrylation pathways for methionine biosynthesis.J Bacteriol 2002 184 1277-86. 

Eikmanns BJ, Metzger M, Reinscheid D, Kircher M, Sahm H. Amplification of three biosynthesis genes in Corynebacterium glutamicum and its influence on carbon flux in different strains. Appl Microbiol Biotechnol 1991 34 617-22. 

Barker HA and Lipmann F (1949) The role of phosphate in the metabolism of Propionibacterium pentosaceum. JBiol Chem 179 247-257 Barksdale L (1970) Corynebacterium diphtheria and its relatives. Bacteriol Rev 34 378-422 Battersby AR (1985) Biosynthesis of the pigments of hfe. Proc R Soc Lond B 225 1-26 Battersby AR (1994) How nature builds the pigments of life the conquest of vitamin B. Science 264 1551-1557... 

Plastourgos S and Vaughn RH (1957) Species of Propionibacterium associated Avith Zapateria spoilage of olives. Appl Microbiol 5 262-271 Pochi PE and Stauss JS (1961) Antibiotic sensitivity of Corynebacterium acnes Propionibacterium acnes). J Invest Dermatol 36 423-429 Polulach OV (1987) Biosynthesis of tetrapyrrole compounds (porphyrins and vitamin 612) by some representatives of genus Propionibacterium. PhD thesis, Moscow State University, Moscow... 

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