Rational Design of Meso-Diaminopimelate Dehydrogenase with Enhanced Reductive Amination Activity for Efficient Production of d-p-Hydroxyphenylglycine.

ABSTRACT: d-p-hydroxyphenylglycine (d-HPG) is an important intermediate in the pharmaceutical industry. In this study, a tri-enzyme cascade for the production of d-HPG from l-HPG was designed. However, the amination activity of Prevotella timonensis meso-diaminopimelate dehydrogenase (PtDAPDH) toward 4-hydroxyphenylglyoxylate (HPGA) was identified as the rate-limiting step. To overcome this issue, the crystal structure of PtDAPDH was solved, and a "binding pocket and conformation remodeling" strategy was developed to improve the catalytic activity toward HPGA. The best variant obtained, PtDAPDH^M4, exhibited a catalytic efficiency (k_cat/K_m) that was 26.75-fold higher than that of the wild type. This improvement was due

SUBMITTER: Tan Y 

PROVIDER: S-EPMC10231207 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature