Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.2.13 (aldolase)
 3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Whole cell biocatalysis is an important tool for pharmaceutical intermediates synthesis, although it is hindered by some shortcomings, such as high cost and toxicity of inducer, mass transfer resistance caused by cell membrane and side reactions. Whole-cell catalysis using N-acetyl-d-glucosamine 2-epimerase (EC 5.1.3.8) and N-acetyl-d-neuraminic acid (Neu5Ac) aldolase (EC 4.1.3.3) is a promising approach for the production of Neu5Ac, a potential precursor of many anti-viral drugs. A powerful catalyst was developed by packaging the enzymes in an engineered bacterium and using a safe temperature-induced vector. Since the mass transfer resistance and the side reactions were substantially reduced, a high Neu5Ac amount (191 mM) was achieved. An efficient method was also presented, which allows one-pot synthesis of Neu5Ac with a safe and economic manner. The results highlight the promise of large-scale Neu5Ac synthesis and point at a potential of our approach as a general strategy to improve whole-cell biocatalysis.
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PMID:One-pot bio-synthesis: N-acetyl-D-neuraminic acid production by a powerful engineered whole-cell catalyst. 2235 59

N-Acetylneuraminic acid is produced by alkaline epimerization of N-acetylglucosamine to N-acetylmannosamine and then subsequent condensation with pyruvate catalyzed by free N-acetylneuraminic acid aldolase. The high-alkaline conditions of this process result in the degradation of reactants and products, while the purification of free enzymes to be used for the synthesis reaction is a costly process. The use of N-acetylglucosamine 2-epimerase has been seen as an alternative to the alkaline epimerization process. In this study, these two enzymes involved in N-acetylneuraminic acid production were immobilized to biopolyester beads in vivo in a one-step, cost-efficient process of production and isolation. Beads with epimerase-only, aldolase-only, and combined epimerase/aldolase activity were recombinantly produced in Escherichia coli. The enzymatic activities were 32 U, 590 U, and 2.2 U/420 U per gram dry bead weight, respectively. Individual beads could convert 18% and 77% of initial GlcNAc and ManNAc, respectively, at high substrate concentrations and near-neutral pH, demonstrating the application of this biobead technology to fine-chemical synthesis. Beads establishing the entire N-acetylneuraminic acid synthesis pathway were able to convert up to 22% of the initial N-acetylglucosamine after a 50-h reaction time into N-acetylneuraminic acid.
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PMID:Bioengineering of bacterial polymer inclusions catalyzing the synthesis of N-acetylneuraminic acid. 2345 47