Stereoselective amino acid synthesis by synergistic photoredox-pyridoxal radical biocatalysis

Developing synthetically useful enzymatic reactions that are not known in biochemistry and organic chemistry is an important challenge in biocatalysis. Through the synergistic merger of photoredox catalysis and pyridoxal 5′-phosphate (PLP) biocatalysis, we developed a pyridoxal radical biocatalysis approach to prepare valuable noncanonical amino acids, including those bearing a stereochemical dyad or triad, without the need for protecting groups. Using engineered PLP enzymes, either enantiomeric product could be produced in a biocatalyst-controlled fashion. Synergistic photoredox-pyridoxal radical biocatalysis represents a powerful platform with which to discover previously unknown catalytic reactions and to tame radical intermediates for asymmetric catalysis. Many enzymes have the ability to perform chemistry beyond the scope of their natural reactions when put together with reactive substrates. Adding light to the mix might be a strategy for broadening reactivity even further by generating radical species. Cheng et al. found that an engineered tryptophan synthase could function together with an organic photocatalyst to produce a range of noncanonical amino acid products, including those with a beta-methyl group, enantio- and diastereoselectively. The authors propose a mechanism in which a radical generated by the photocatalyst intercepts an aminoacrylate intermediate in a reaction cycle that partially parallels the natural reaction. —Michael A. Funk Stereoselective synthesis of noncanonical amino acids is achieved by photoredox biocatalysis.