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 inste

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