Threonine aldolase-catalyzed aldol

T. Nishiyama, S.S. Mobile, T. Kajimoto, M. Node, Synthesis of thymine polyoxin C by using L-threonine aldolase-catalyzed aldol reaction. Heterocycles 71 (2007) 1397-1405. 

Fujii, M., Miura, T., Kajimoto, T., and Ida, Y., Facile S5mthesis of 3,4-dihydroxyprolines as an application of the L-threonine aldolase-catalyzed aldol reaction. Sunlett 2000, 7, 1046-1048. 

Threonine Aldolase-Catalyzed Aldol Reactions Using Giycine and an Aidehyde... 

Nishiyama T, Kajimoto T, Mobile SS, Hayama N, Otsuda T, Ozeki M, Node M. The first enantioselective synthesis of imino-deoxydigitoxose and protected imino-digitoxose by using L-threonine aldolase-catalyzed aldol condensation. Tetrahedron Asymm. 2009 20 230-234. 

Figure 10.45 Aldol reactions catalyzed in vivo by serine hydroxymethyl transferase and by threonine aldolases.

The metabolism of P-hydroxy-a-amino adds involves pyridoxal phosphate-dependent enzymes, dassified as serine hydroxymethyltransferase (SHMT) (EC 2.1.2.1) or threonine aldolases (ThrA L-threonine selective = EC 4.1.2.5, L-aHo-threonine selective = EC 4.1.2.6). Both enzymes catalyze reversible aldol-type deavage reactions yielding glycine (120) and an aldehyde (Eigure 10.45) [192]. 

PLP-dependent enzymes catalyze the following types of reactions (1) loss of the ce-hydrogen as a proton, resulting in racemization (example alanine racemase), cyclization (example aminocyclopropane carboxylate synthase), or j8-elimation/replacement (example serine dehydratase) (2) loss of the a-carboxylate as carbon dioxide (example glutamate decarboxylase) (3) removal/replacement of a group by aldol cleavage (example threonine aldolase and (4) action via ketimine intermediates (example selenocysteine lyase). 

The glycine-dependent aldolases are pyridoxal 5-phosphate dependent enzymes that catalyze the reversible aldol reaction, where glycine and an acceptor aldehyde form a (i-hydroxy-a-amino acid (Scheme 5.47).74 Serine hydroxymethyltransferases, SHMT (EC 2.1.2.1), and threonine aldolases, two types of glycine dependent aldolases, have been isolated. In... 

The enzymatic aldolization of (/ )-glyceraldehyde acetonide with glycine catalyzed by L-threonine aldolase from Candida humicola gave the key intermediates for the synthesis of 3,4-dihydroxyprolines in six steps (Fujii et al. 2000). 

Scheme 2.196 Aldol reactions catalyzed by L-threonine aldolase...

Aldol reactions have been catalyzed by aldolases as well as by catalytic antibodies. For example, L-threonine aldolase was applied to C—C bond formation of an aldehyde with glycine. The resulting adduct could be further converted to a precursor of N-acetyl-4-deoxy-D-mannosamine, a potent inhibitor of N-acetylneuraminic acid synthetase (Fig. 10.39(a)). "... 

The metabolism of j5-hydroxy-a-amino acids involves pyridoxal phosphate-dependent enzymes, classified as serine hydroxymethyltransferase or threonine aldolases, that catalyze reversible aldol-type cleavage to aldehydes and glycine (134) [284]. 

An antibody that mimics threonine aldolase, which uses pyridoxal as the cofactor to catalyze the aldol reaction of glycine with aldehydes, has also been reported. Antibody 10H2 catalyzed the retro-aldol reaction of jd-hydroxy-a-amino acid in the presence of pyridoxal [55]. 

Threonine aldolases (ThrA EC4.1.2.5) and serine hydroxymethyltransferases (SHMT EC 2.1.2.1) are pyridoxal-5 -phosphate (PEP) dependent aldolases that catalyze the aldol addition of glydne to aldehydes [155-158], Since two new stereogenic centers are formed, four possible stereoisomers can be formally obtained. However, contrary to the case of DHAP-dependent aldolases, the four set of stereocomplementary enzymes have not been found in nature yet (Scheme 10.7) [157,159,160]. 

Aldol addition of glycine to aldehydes catalyzed by threonine aldolases. PLP, Pyridoxal-5 -phosphate. 

The pyridoxal-5 -phosphate-dependent threonine aldolases (ThrA EC 4.1.2.5) and serine hydroxymethyltransferase (SHMT EC 2.1.2.1) catalyze the aldol addition of glycine to aldehydes with the formation of two new stereogenic centers [15,44,161-163]. Hence, four possible products can be formally obtained from a single aldehyde, depending on the specificity of the threonine aldolase. All glycine aldolases assayed... 

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