초록
<P>Enantiomerically pure amino acid derivatives could be foundational compounds for peptide drugs. Deracemization of racemates to <SMALL>L</SMALL>-amino acid derivatives can be achieved through the reaction of evolved <SMALL>D</SMALL>-amino acid oxidase and chemical reductants, whereas deracemization to <SMALL>D</SMALL>-amino acid derivatives has not progressed due to the difficulty associated with the heterologous expression of <SMALL>L</SMALL>-amino acid oxidase (LAAO). In this study, we succeeded in developing an ancestral LAAO (AncLAAO) bearing broad substrate selectivity (13 <SMALL>L</SMALL>-amino acids) and high productivity through an <I>Escherichia coli</I> expression system (∼50.7 mg/L). AncLAAO can be applied to perform deracemization to <SMALL>D</SMALL>-amino acids in a similar way to deracemization to <SMALL>L</SMALL>-amino acids. In fact, full conversion (>99% ee, <SMALL>D</SMALL>-form) could be achieved for 16 racemates, including nine <SMALL>D</SMALL>,<SMALL>L</SMALL>-Phe derivatives, six <SMALL>D</SMALL>,<SMALL>L</SMALL>-Trp derivatives, and a <SMALL>D</SMALL>,<SMALL>L</SMALL>-phenylglycine. Taken together, we believe that AncLAAO could be a key enzyme to obtain optically pure <SMALL>D</SMALL>-amino acid derivatives in the future.</P><BR>[FIG OMISSION]</BR>