Glyoxylate shunt and

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...

McKinney JD, Honer zu Bentrup K, Munoz-Elias EJ et al. Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 2000 406[6797] 735—738. 

Fig. 9. Pathway duplication the methyl citrate cycle and the glyoxylate shunt. A pathway for acetate metabolism in E. coli that uses the glyoxylate shunt is depicted on the right. Part of the methyl citrate cycle, a pathway for propionate metabolism, is depicted on the left. The pathways are analogous furthermore, three of the four steps are catalyzed by homologous enzymes. PrpE (propionyl-CoA synthase) is homologous to AcsA (acetyl-CoA synthase). PrpC (2-methyl-citrate synthase) is homologous to GltA (citrate synthase). PrpB (2-methyl-isocitrate lyase) is homologous to AceA (isocitrate lyase). The third step in the methyl citrate cycle has been suggested to be catalyzed by PrpD the second half of the reaction (the hydration) can be catalyzed by aconitase.

Certain microorganisms have a modification of this cycle in which isocitric acid is cleaved to succinic acid and glyoxylic acid. The latter acid is condensed with acetyl-CoA to form malic acid. In this modification (the glvoxvlic acid cvcle), oxalsuccinic acid and alpha-ketoglularic acid are not involved. This is sometimes referred to as the glyoxylate shunt pathway. 

Figure 4a. Major metabolic pathways in M. ammoniaphilum involving glucose, acetate, and glutamate. Glucose labeled at C-1 produces [3- C] pyruvate via the Embden-Meyerhof pathway (EMP) and unlabeled pyruvate via the hexose monophosphate shunt (HMS). [3- C] pyruvate enters the tricarboxylic acid (TCA) and glyoxylate shunt (GS) cycles as [3- C] oxaloacetate and/or [2- C] acetate and can result in the formation of [2- C] glutamate, [4- C] glutamate, and [2,4A C] glutamate via a-ketoglutorate formed in 1/3 of a turn of the TCA cycle. Formation of glutamate after one or more turns of the TCA cycle will tend to randomize the label because of the formation of the symmetrical intermediates succinate...

Elucidation of the metabolic pathway repertoire of C, glutamicum was initiated soon after its discovery [4-6], related to the high importance of the central metabolism for amino acid fermentation. Evidence on the presence of the major catabolic routes, such as the Embden-Meyerhof-Parnas (EMP) pathway, the pentose phosphate (PP) pathway, the tricarboxylic acid (TCA) cycle, and the glyoxylate shunt had already been provided by the end of the 1950s [4, 5, 7] (Figure 6.1). However, it took more than 30 years for a more detailed resolution of the central metabolic network mainly related to the complex structure of the phosphoenolpyruvate/pyruvate - oxaloacetate/malate node [8-11]. Altogether,... 

Figure 8.4 Biosynthetic potentiai of Pseudomonas putida. Extended carbon core metabolism of Pseudomonas putida KT2440 including the major catabolic routes of Entner-Doudoroff pathway, Embden-Meyerhof-Parnas pathway, pentose phosphate pathway, tricarboxylic acid cycle, glyoxylate shunt, anaplerotic reactions, fatty acid de novo biosynthesis, p-oxidation of fatty acids, as well as the convergent -ketoadipate pathway for catabolism of aromatics. Known pathways for respective precursor supply for the broad product spectrum of P. putida KT2440 are indicated by light red arrows. Natural products and substrates are highlighted in black, heterologous products and substrates In red.

The pathways in the central carbon metabolism involve TCA cycle and glyoxylate shunt, glycolysis, phosphotransferase system (PTS), gluconeogenesis, pentose phosphate pathway (PPP).The carbon flux partitions at different nodes in the central metabolism and major flux partitioning for the product of interest may occur at principal branch points. Engineering of the enzymes in these branch points of the biosynthetic pathways will direct the carbon flux toward the product of interest leading to maximal product yield. 

Tricarboxylic acid (TCA) cycle and glyoxylate shunt. It is known that the oxidative capacity of bacteria is the result of co-ordinated work of the enzymes of glycolysis, TCA cycle, hexose monophosphate shunt, electron transport in the respiratory chain, and flavin respiration. It was shown (Krainova and Bonarceva, 1973) thatP. petersonii and P. shermanii, grown on glucose, contain all the enzymes of the TCA cycle (Fig. 3.7) and... 

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