d-Tryptophan and its derivatives are important precursors of a wide range of indole-containing pharmaceuticals and natural products. Here, we developed a one-pot biocatalytic process enabling the synthesis of d-tryptophans from indoles in good yields and high enantiomeric excess (91% to >99%). Our method couples the synthesis of l-tryptophans catalyzed by Salmonella enterica tryptophan synthase with a stereoinversion cascade mediated by Proteus myxofaciens l-amino acid deaminase and an aminotransferase variant that we engineered to display native-like activity toward d-tryptophan. Our process is applicable to preparative-scale synthesis of a broad range of d-tryptophan derivatives containing electron-donating or -withdrawing substituents at all benzene-ring positions on the indole group.

One-Pot Biocatalytic Synthesis of Substituted D-Tryptophans from Indoles Enabled by an Engineered Aminotransferase

Parmeggiani F.;
2019

Abstract

d-Tryptophan and its derivatives are important precursors of a wide range of indole-containing pharmaceuticals and natural products. Here, we developed a one-pot biocatalytic process enabling the synthesis of d-tryptophans from indoles in good yields and high enantiomeric excess (91% to >99%). Our method couples the synthesis of l-tryptophans catalyzed by Salmonella enterica tryptophan synthase with a stereoinversion cascade mediated by Proteus myxofaciens l-amino acid deaminase and an aminotransferase variant that we engineered to display native-like activity toward d-tryptophan. Our process is applicable to preparative-scale synthesis of a broad range of d-tryptophan derivatives containing electron-donating or -withdrawing substituents at all benzene-ring positions on the indole group.
amino acids; biocatalysis; enzymes; organic synthesis; protein engineering; rational design
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11311/1126292
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