Engineering Streptomyces coelicolor Carbonyl Reductase for Efficient Atorvastatin Precursor Synthesis.

ABSTRACT: Streptomyces coelicolor CR1 (ScCR1) has been shown to be a promising biocatalyst for the synthesis of an atorvastatin precursor, ethyl-(S)-4-chloro-3-hydroxybutyrate [(S)-CHBE]. However, limitations of ScCR1 observed for practical application include low activity and poor stability. In this work, protein engineering was employed to improve the catalytic efficiency and stability of ScCR1. First, the crystal structure of ScCR1 complexed with NADH and cosubstrate 2-propanol was solved, and the specific activity of ScCR1 was increased from 38.8 U/mg to 168 U/mg (ScCR1_I158V/P168S) by structure-guided engineering. Second, directed evolution was performed to improve the stability using ScCR1_I158V/P168S as

SUBMITTER: Li M 

PROVIDER: S-EPMC5452830 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature