Nitroalkanes as Versatile Nucleophiles for Enzymatic Synthesis of Noncanonical Amino Acids
David K Romney1, Nicholas S Sarai1, Frances H Arnold1
1Division of Chemistry and Chemical Engineering 210-41, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, United States.
Abstract:
C-C bond-forming reactions often require nucleophilic carbon species rarely compatible with aqueous reaction media, thus restricting their appearance in biocatalysis. Here we report the use of nitroalkanes as a structurally versatile class of nucleophilic substrates for C-C bond formation catalyzed by variants of the β-subunit of tryptophan synthase (TrpB). The enzymes accept a wide range of nitroalkanes to form noncanonical amino acids, here the nitro group can serve as a handle for further modification. Using nitroalkane nucleophiles greatly expands the scope of compounds made by TrpB variants and establishes nitroalkanes as a valuable substrate class for biocatalytic C-C bond formation.
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