Method for asymmetrically synthesizing (2S,3R)-p-methylsulfonylphenylserine by one-bacterium multi-enzyme whole cells

Abstract

The invention provides a method for asymmetrically synthesizing (2S,3R)-p-methylsulfonylphenylserine by one-bacterium multi-enzyme whole cells, which belongs to the field of biocatalysis and enzyme engineering. By simultaneously expressing L-threonine transferase (PsLTTA), ethanol dehydrogenase (ApADH) and formate dehydrogenase (CbFDH) in escherichia coli BL21 (DE3) engineering bacteria, asymmetric efficient biosynthesis of (2S,3R)-p-methylsulfonylphenylserine is realized. The key chiral building block (2S,3R)-p-methylsulfonylphenylserine of the beta-amino alcohol antibiotics can be obtained through one-step reaction at normal temperature and normal pressure, meanwhile, the inhibition effect of a byproduct acetaldehyde on the PsLTTA is relieved, and the method is an efficient green biosynthesis way.

Description

technical field [0001] The invention belongs to the field of biocatalysis and enzyme engineering, and specifically relates to a method for asymmetrically synthesizing (2S, 3R)-p-thiamphenicol phenylserine in whole cells with "one bacterium and multiple enzymes". Background technique [0002] (2S,3R)-P-thymphenylphenylserine is a key chiral building block for the synthesis of β-aminoalcohol antibiotics florfenicol and thiamphenicol. In 2015, China’s export volume of β-aminoalcohol antibiotics alone exceeded 2,700 tons, a year-on-year increase of 9.2%, and the export value reached 186 million US dollars, ranking among my country’s top 10 export drugs. Therefore, the establishment of a fast, efficient and green synthetic route to (2S,3R)-p-thymphenylphenylserine has broad application prospects. [0003] At present, the main method of large-scale production of (2S,3R)-p-thiamphenicol phenylserine at home and abroad is to use p-thiamphenicol benzaldehyde and glycine as raw mater...

AI Technical Summary

Problems solved by technology

Although the reaction route is simple and suitable for industrial production, there are the following problems: 1. The reaction conditions are severe, and strong acid and strong base are used simultaneously; 2. The expensive chiral resolution reagent D-tartaric acid is required

The operation is cumbersome and time-consuming, the production cost is high, and the method adopts the method of chiral resolution instead of the asymmetric catalytic synthesis method, and the yield of the target product is low, only 50%

[0008] Therefore, there is a lack of a high-efficiency synthesis technology of (2S,3R)-p-thiamphenicol phenylserine that is easy to operate, short in reaction time, does not require enzyme fermentation production and purification preparation process, and is more conducive to industrial production and application.

Images