Enzymatic hydrolysis of racemic a-substituted 4-methylthiobutyro

Details Enzymatic hydrolysis of racemic a-substituted 4-methylthiobutyro Enzymatic hydrolysis of racemic a-substituted 4-methylthiobutyro

1997-03-20

1998-09-29

Saucier, Sandra E.

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Preparing sulfur-containing organic compound

822829, 822146, C12P 1100

Patent

active

058144978

DESCRIPTION:

BRIEF SUMMARY
The present invention relates to the use of a nitrilase as a catalyst for hydrolysing a nitrile group into a carboxylic group. The invention relates more precisely to the use of the nitrilase chosen from nitrilases of microorganisms of the genus Alcaligenes, Rhodococcus or Gordona and more precisely of Alcaligenes faecalis deposited under the number ATCC 8750, Rhodococcus sp. HT 29-7 deposited under the number FERM BP-3857 or Gordona terrae MA-1 deposited under the number FERM BP-4535.
The nitrilase of Alcaligenes faecalis is described, for example, in the European and Japanese patents published under the numbers EP 348,901 and JP 03 224 496 respectively, both belonging to the Asahi company. In these patents, and more particularly in the European patent, the nitrilase is used to produce optically active acids from racemic nitriles. The preferred starting nitriles are .alpha.-substituted and contain an alkyl chain preferably containing 1 to 3 carbon atoms or an aromatic radical. Example 11 of the abovementioned European patent describes the hydrolysis of racemic mandelonitrile with Alcaligenes faecalis; the R-(-)-mandelic acid is obtained in an enantiomeric excess of 91%. European patent 486,289 and its equivalent American patent U.S. Pat. No. 5,326,702 from the company Nitto Chemical describe the use of Alcaligenes sp. BC35-2 (FERM No. 11265 or FERM-BP-3318) to hydrolyse mandelonitrile in the presence of a sulphite; in this case, mandelic acid is obtained in an enantiomeric excess of about 98%.
Patent JP 04 341 185 from the company Asahi also describes the preparation and use of the nitrilase from Alcaligenes faecalis ATCC 8750 to solve the problems of preparation of optically pure compounds from their racemic nitrile. The enantioselective nitrilase described in the Japanese patent referred to above is more preferably capable of hydrolysing the 2-hydroxynitrile of general formula (I) below into 2-hydroxycarboxylic acid of formula (II) below: ##STR1## in which R represents an optionally substituted aryl group or an optionally substituted heterocyclic group. It is mentioned in that patent that hydrolysis of the nitrile of mandelic acid by the said nitrilase makes it possible to obtain a 100% enantiomeric excess of R-(-)-mandelic acid. It is mentioned in Example 5 that the said nitrilase may be used to hydrolyse aliphatic nitrites such as valeronitrile, acrylonitrile, 2-halopropionitriles and chloroacetonitrile. Nothing is specified as regards the enantioselectivity of this hydrolysis on aliphatic nitriles having an asymmetric centre.
The said text also specifies that the nitrilase of Alcaligenes faecalis is of optimum activity at a pH between 6.5 and 8.0; the working temperature of the said enzyme should, according to that reference, always be below 45.degree. C.
It appeared to be entirely surprising that the said enzyme of Alcaligenes faecalis ATCC 8750, when used to hydrolyse 4-methylthio-2-hydroxybutyronitrile, carried out this hydrolysis without any selectivity from the point of view of the optical purity. This enzyme hydrolyses the said nitrile producing a racemic mixture of the two acids with no preponderance of either of the isomers.
The nitrilase of Rhodococcus sp. HT 29-7 deposited under the number FERM BP-3857 is described, for example, in the European and American patents published under the numbers EP 610,049 and U.S. Pat. No. 5,296,373 respectively, both belonging to the company Nitto.
In these patents, and particularly in the American patent, the nitrilase is used to produce optically active acids from racemic nitriles bearing a phenyl group. The starting nitriles all contain an aromatic radical; this essentially involves hydrolysis of mandelonitrile or of derivatives thereof substituted on the aromatic ring. Example 1 of the abovementioned American patent describes the hydrolysis of racemic mandelonitrile with Rhodococcus sp. HT 29-7; the R-(-)-mandelic acid is obtained in an enantiomeric excess of 100%. Example 2 describes the hydrolysis of substituted mandelonitrile derivatives on the ring;

REFERENCES:
Bhalla et al., "Asymmetric hydrolysis of alpha aminonitriles to optically active amino acids by a nitrilase of Rhodococcus rhodochrous PS-34", Appl. Microbiol. Biotechnol. 37(2):184-90 (1992).
ATCC Bacteria and Bacteriophages, p. 157 (1992).
Chemical Abstract, vol. 117:46744h, Aug. 3, 1992.
Chemical Abstract, vol. 116:254079x, Jun. 22, 1992.

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