Improvements of shikimic acid production in Escherichia coli with ideal metabolic modification in biosynthetic pathway—A review

Abstract:

Abstract:Shikimic acid(SA) is an important intermediate in the synthesis of aromatic amino acids and has emerged as a key chiral starting material for the synthesis of antiviral drug oseltamivir phosphate(Tamiflu)．Microbial production of SA has a variety of advantages，and E．coli is commonly applied in large-scale fermentation and industrial production．Metabolic engineering is one of the main technical methods to construct the industrialized high-yield shikimic acid producing strains．Phosphoenolpyruvate: carbohydrate phosphotransferase system (PTS) is the major active transport system involved in the glucose internalization and phosphorylation in E．coli in which it affects the use ratio of PEP in cell．Modification and transformation of the PTS system could regulate the flow of intracellular metabolism and reduce the waste of PEP caused by the PTS system，in the same time，a more ideal shikimic acid producing strain can be constructed combined with the specific modifications of metabolic pathways．It was reported that in the 10 L system，shikimic acid yield reached up to 0.36 mol/mol，with concentration up to 84 g/L．This paper takes a brief overview of the metabolic engineering in the shikimic acid pathway and the transformation of the glucose transporter system，summarizes some latest researches and developments in recent years.