Chemoenzymatic Synthesis of Ubiquitous Biological Redox Cofactors

Redox cofactors are utilized by a myriad of proteins, ranging from metabolic enzymes to those performing post-translational modifications. Labeled redox cofactors have served as a vital tool for a broad range of studies. This account describes chemoenzymatic syntheses of the isotopically labeled, biologically important redox cofactors: nicotinamide adenine dinucleotide, methylene tetrahydrofolate, and flavin nucleotides. An overview of the general strategy is presented. These examples demonstrate the utility of enzymatic synthesis. 1 Introduction 2 Nicotinamide Cofactors 2.1 Synthesis of Remote-Labeled C-14-NADPH 2.1.1 Synthesis of [Ad-C-14] NADPH 2.1.2 Synthesis of [Carbonyl-C-14] NADPH 2.2 Synthesis of S- and R-[4-H-3] NADPH 2.2.1 One-Step S- and Three-Step R-[4-H-3] NADPH Synthesis 2.2.2 One-Pot, One-Step R-[4-H-3] NADPH Synthesis 2.3 Synthesis of S- and R-[Ad-C-14, 4-H-2] NADPH 2.3.1 One-Step S-, Three-Step R-[Ad-C-14, 4-H-2] NADPH Synthesis 2.3.2 One-Pot, One-Step R-[Ad-C-14, 4-H-2] NADPH Synthesis 3 Methylene Tetrahydrofolate 4 Flavin Nucleotides 5 Conclusions and Outlook