Thiamin diphosphate in biological chemistry: exploitation of diverse thiamin diphosphate‐dependent enzymes for asymmetric chemoenzymatic synthesis

Abstract

Thiamin diphosphate-dependent enzymes participate in numerous biosynthetic pathways and catalyse a broad range of reactions, mainly involving the cleavage and formation of C-C bonds. For example, they catalyse the nonoxidative and oxidative decarboxylation of 2-keto acids, produce 2-hydroxy ketones and transfer activated aldehydes to a variety of acceptors. Moreover, they can also catalyse C-N, C-O and C-S bond formation. Because of their substrate spectra and different stereospecificity, these enzymes extend the synthetic potential for asymmetric carboligations appreciably. Different strategies have been developed to identify new members of this promiscuous enzyme class and the reactions they catalyse. This enabled us to introduce solutions for longstanding synthetic problems, such as asymmetric cross-benzoin condensation. Moreover, through a combination of protein structure analysis, enzyme and substrate engineering, and screening methods we explored additional stereochemical routes that have not been described previously for any of these interesting enzymes.

Diversity‐Oriented Production of Metabolites Derived from Chorismate and Their Use in Organic Synthesis

“…[38] The microbial production of uncommon structures derived from chorismate (such as echinosporin) [39] becomes feasible as demonstrated by the thiamine diphosphate (ThDP)-dependent MenD-catalyzed CÀC bond formation resulting in the production of 6. Given the multipurpose activity and broad substrate range of ThDP-dependent enzymes, [40] it is justified to suppose that MenD variants or other ThDPdependent enzymes will accept chorismate, isochorismate, and derivatives as a substrate. This will result in the formation of natural and novel non-natural metabolites such as 27.…”

Substrate Specificity of Thiamine Pyrophosphate-Dependent 2-Oxo-Acid Decarboxylases in Saccharomyces cerevisiae

“…Therefore, the observation that aro10⌬ mutants are still able to decarboxylate phenylpyruvate indicates that at least one of the PDCs has a substrate spectrum that allows the decarboxylation of substrates other than pyruvate. The kinetic properties of PDCs originating from different microorganisms were compared previously (41). However, a systematic comparison of the substrate specificity of the individual 2-oxo-acid decarboxylases in S. cerevisiae is not available, and previous biochemical studies of PDC in this yeast, which indicated a broad substrate specificity (33,51), were likely to have been based on mixtures of the three Pdc isoenzymes (34), possibly contaminated with Aro10 (12).…”

Importance of the Tpk Gene Phylogenetic Relationships of the Thiamine Biosynthesis Pathway for the Study of Plant Evolution Phylogeny of the TPK gene in plants

“…Vitamin B1 (Thiamine) is a coenzyme required by all organisms. The active form, thiamin diphosphate (TDP), is an essential cofactor for enzymes of key metabolic pathways, such as glycolysis, acetyl-CoA synthesis, Krebs cycle, alcoholic fermentation, pentose's-phosphate pathway, Calvin cycle , branched chain amino acid pathway and biosynthesis of pigments in photosynthetic organisms [2,3].…”