Efficient production of salvianic acid A from L-dihydroxyphenylalanine through a tri-enzyme cascade.

ABSTRACT: Salvianic acid A (SAA), used for treating cardiovascular and cerebrovascular diseases, possesses several pharmacological properties. However, the current methods for the enzymatic synthesis of SAA show low efficiency. Here, we constructed a three-enzyme cascade pathway in Escherichia coli BL21 (DE3) to produce SAA from L-dihydroxyphenylalanine (L-DOPA). The phenylpyruvate reductase (LaPPR) from Lactobacillus sp. CGMCC 9967 is a rate-limiting enzyme in this process. Therefore, we employed a mechanism-guided protein engineering strategy to shorten the transfer distances of protons and hydrides, generating an optimal LaPPR mutant, LaPPR^Mu2 (H89M/H143D/P256C), with a 2.8-fold increase in specific activity and 9.3-time increase in k_cat/K_m value compared to that

SUBMITTER: Yang J 

PROVIDER: S-EPMC10992476 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature