Nonheme Fe 1,3-nitrogen migratases for asymmetric noncanonical amino acid synthesis.

Nonheme Fe enzymes are biologically important enzymes that use iron at their active site without incorporating a heme cofactor. Nonetheless, these enzymes remain largely underexploited in the development of new-to-nature biocatalytic reactions with synthetic utility. Here we report the repurposing and directed evolution of plant-derived nonheme Fe enzyme 1-aminocyclopropane-1-carboxylic acid oxidase into a nitrogen migratase to enable the efficient and enantioselective 1,3-nitrogen migration reaction on both secondary C(sp)-H and tertiary C(sp)-H bonds from racemic substrates.

Biocatalytic enantioselective C(sp)-H fluorination enabled by directed evolution of non-haem iron enzymes.

Due to the scarcity of C-F bond forming enzymatic activities in nature and the contrasting ubiquity of organofluorine moieties in bioactive compounds, developing new biocatalytic fluorination reactions represents a preeminent challenge in enzymology, biocatalysis, and synthetic biology. Additionally, catalytic asymmetric C(sp)-H fluorination remains a challenging problem facing synthetic chemists. Although many nonheme Fe halogenases have been discovered to promote C(sp)-H halogenation reactions, to date, efforts to convert these Fe halogenases to fluorinases have remained unsuccessful.

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.

Nitric oxide donor, V-PROLI/NO, provides protection against arsenical induced toxicity in rat liver cells: requirement for Cyp1a1.

Arsenic is a cancer chemotherapeutic but hepatotoxicity can be a limiting side effect. O(2)-vinyl 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (V-PROLI/NO) is a nitric oxide (NO) donor prodrug and metabolized by liver cytochromes P450 (CYP450) to release NO. The effects of V-PROLI/NO pretreatment on the toxicity of arsenic (as NaAsO(2)) were studied in a rat liver cell line (TRL 1215).