Metabolism artificial

The most convenient method is the formation of two equivalents of (25) by retro-aldol cleavage from commercially available (26) by the combined action of FruA and triose phosphate isomerase (Figure 10.18 inset) [84]. This scheme has been extended into a highly integrated, artificial metabolism for the efficacious in situ preparation of (25) from inexpensive feedstock such as glucose and fructose (two equivalents of... 

Figure 10.18 Enzymatic in situ generation of dihydroxyacetone phosphate from fructose 1,6-bisphosphate (b), with extension to an in vitro artificial metabolism for its preparation from inexpensive sugars alongthe glycolysis cascade (a), and utilization for subsequent stereoselective carbon-carbon bond formation using an aldolase with distinct stereoselectivity (c).

Scheme 10. Artificial metabolism for the in situ preparation of DHAP from regenerable carbohydrate resources...

Scheme 11. Metabolic engineering of an artificial metabolism for stereoselective C-C bond formation by selecting appropriate catalysts...

Fessner, W.-D. and Walter, C. (1992) Artificial metabolisms for the asymmetric one-pot synthesis of branched-chain saccharides. Angew. Chem. Int. Ed. Engl., 31, 614-616. 

Since enzymes generally function under the same or similar conditions, several biocatalytic reactions can be carried out in a reaction cascade in a single flask. Thus, sequential reactions are feasible by using multienzyme systems in order to simplify reaction processes, in particular if the isolation of an unstable intermediate can be omitted. Furthermore, an unfavorable equilibrium can be shifted towards the desired product by linking consecutive enzymatic steps. This unique potential of enzymes is increasingly being recognized as documented by the development of multienzyme systems, also denoted as artificial metabolism [15]. 

Scheme 3.17 Artificial metabolic pathway composed by an alcohol dehydrogenase (LK-ADH), an enoate reductase (XenB), and a Baeyer-Villiger monooxygenase (BVMO j gj ) different substrate types that have been successfully converted to chiral products via this pathway.

Banta S, Swanson BA, Wu S, Jamagin A, Anderson S (2002) Optimizing an artificial metabolic pathway engineering the cofactor specificity of Corynebacterium 2,5-diketo-D-gluconic acid reductase for use in vitamin C biosynthesis. Biochemistry 41 6226-6236 Bremus C, Herrmann U, Biinger-Meyer S, Sahm H (2006) The use of microorganisms in L-ascorbic acid production. J Biotechnol 124 196-205... 

Multi-enzymatic artificial metabolism for in-situ generation of dihydroxyacetone phosphate from inexpensive sugars. 

Artificial metabolic stimulants, such as di-nitrophenol, are also effective in raising the metabolic rate to the normal level when administered to myxcedematous subjects, but fail to benefit the other associated disturbances, which is additional proof that the thyroid gland action controls other processes in addition to its calorigenic action. 

In some cases, multienzyme cascades are used where an artificial metabolic pathway has been created on an electrode to take a specific substrate and electrocataly tic ally convert it to produce energy [5,12-14]. With these systems, coulometry is useful for determining coulombic efficiency, as well as combining coulometry with nuclear magnetic resonance (NMR) analysis to determine reaction intermediates and products, and elucidate bottlenecks in the artificial metabolic pathway, or to determine the energy density of a fuel cell. Please refer to Chapter 5 for further information regarding multienzyme cascades. 

W.-D. Fessner, C. Walter, Enzymes in organic synthesis. 3. Artificial metabolism applied to the one-pot asymmetric synthesis of branched saccharides, Angew. Chem. Int. 31 (1992) 614-616. 

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