Production of chiral alpha-hydroxy acid and its strain by using biological catalysis method

Abstract

The invention provides a novel strain of (S) producing-mandelic acid dehydrogenase, that is, Pseudomonas aeruginosa ZJB1125, which is preserved in the China Center for Type Culture Collection with the preservation number CCTCC No:M 2011394 on 13 November 2011 in Wuhan University, Wuhan, China, 430072. (R)-mandelic acid and related derivatives with high optical purity prepared by the strain of the invention have the high optical purity of more than 99 %, and both the yield and corresponding oxidation product ketonic acid yield of being close to 50 %. By using the strain of the invention to split alpha-hydroxy acid raceme, the advantages of simple and safe operation, low cost, mind reaction conditions and the like are achieved, more importantly, the atom economy of the process is significantly raised, and the invention has good industrial application prospects.

Description

(1) Technical field [0001] The present invention relates to a new bacterial strain producing (S)-mandelate dehydrogenase - Pseudomonas aeruginosa (Pseudomonas aeruginosa) ZJB1125, and its preparation of corresponding (R) - Alpha-hydroxyacids and their use in ketoacids. (2) Background technology [0002] Optically active α-hydroxy acids refer to a class of compounds with hydroxyl and carboxyl groups on the chiral carbon. They are important chiral "building blocks" and can be used for the asymmetric synthesis of a large number of bioactive molecules. Among these compounds, optically pure mandelic acid is considered to be the most important representative from a commercial point of view. Mandelic acid is also known as a-hydroxyphenylacetic acid, mandelic acid, and mandelic acid. The structural formulas of its R-type and S-type are as follows: [0003] [0004] Optically active mandelic acid and its derivatives are extremely important pharmaceutical intermediates: such as R...

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Problems solved by technology

[0007] At present, the preparation of optically active mandelic acid and its derivatives mainly adopts the chemical resolution method of the racemate: first synthesize the racemate of mandelic acid, and then use a certain method to resolve it. The method of resolution is mainly There are the following types: ①Diastereomeric salt crystallization resolution method, the common problem faced is that it is expensive and has certain toxicity, which causes waste of resources and environmental pollution to a certain extent. At present, the large-scale production of R in my country -Mandelic acid is produced by this method

② Chromatographic separation method, the equipment cost of this method is too high, the consumption is large, the cost is too high, and the processing capacity is small, so it is limited to detection and laboratory preparation, and cannot be used for commercial production

④The capillary electrophoresis separation method is widely used in the separation of various drug enantiomers due to its high efficiency, rapidity, and economy. This method has disadvantages such as high cost

[0013] The reported strains all have problems such as low activity, long reaction time, and low conversion rate, and are difficult to industrialize

In addition, the α-keto acid obtained by the catalytic reaction is an important intermediate of microbial metabolism, which will be further degraded and difficult to accumulate during the reaction process. It is impossible to simultaneously prepare optically active mandelic acid and its derivatives and corresponding Keto acids, resulting in poor atom economy

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