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 Biological process for producing .alpha.-hydroxyamide or .alpha.-hydroxy acid

Details
Inventors: Endo, Takakazu; Yamagami, Tomohide; Tamura, Koji;
Assignee: Nitto Chemical Industry Co., Ltd. (Tokyo, JP)
Primary Examiner: Lilling; Herbert J.
Assistant Examiner:
Attorney, Agent or Firm: Sughrue, Mion, Zinn, Macpeak & Seas

A process for biologically producing an .alpha.-hydroxyamide or an .alpha.-hydroxy acid represented by formula (III) ##STR1## wherein R represents a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aryloxy group or a substituted or unsubstituted and saturated or unsaturated heterocyclic group; and X represents an amido group or a carboxyl group, comprising reacting an .alpha.-hydroxynitrile represented by formula (I): ##STR2## wherein R is as defined above, or a mixture of an aldehyde represented by formula (II): R--CHO (II) wherein R is as defined above, and hydrogen cyanide with a microorganism capable of producing such an amide or acid from the corresponding .alpha.-hydroxynitrile is disclosed, in which the reaction system contains a sulfite ion, a disulfite ion or a dithionite ion. The enzymatic activity of the microorganism lasts for an extended period of time.

DETAILED DESCRIPTION OF THE INVENTION A sulfite ion, a disulfite ion or a dithionite ion added to the reaction system is supplied as, for example, sodium sulfite, sodium bisulfite, sodium dithionite, potassium sulfite, potassium bisulfite, potassium dithionite, ammonium sulfite, ammonium bisulfite or ammonium dithionite.
The following mechanism is suggested to account for the action of those ions.
A sulfite ion, a disulfite ion or a dithionite ion has properties of forming a complex with an aldehyde.
That is, those ions rapidly react with an aldehyde released by dissociation of an .
alpha.
-hydroxynitrile in a polar solvent to form a complex, thus serving to maintain a low free aldehyde concentration in the reaction system.
The complex formed undergoes a nucleophilic reaction with a proton or hydrogen cyanide to release reversibly an aldehyde or an .
alpha.
-hydroxynitrile, respectively.
According to the present invention, hydration or hydrolysis of a nitrile can be carried on while maintaining a low aldehyde concentration in the reaction system by a combination of those actions so that the enzyme inhibitory action of the aldehyde is minimized and the reaction can last for an extended period of time, in a stable manner, without causing drastic deactivation of the enzyme making it possible to accumulate the produced amide or acid in high concentrations.
It is still obscure, however, whether the enzyme stabilization mechanism by a sulfite ion, a disulfite ion or a dithionite ion is attributable only to the reduction in free aldehyde concentration in the reaction system.
Considering the above-stated fact that an aldehyde generally has properties of binding to proteins to deactivate an enzyme, it appears that the inhibitory effect on enzyme activity by a sulfite ion, a disulfite ion or a dithionite ion applies to all biological reactions which involve an aldehyde.
In other words, the microorganism which can be used in the production of an amide or an acid from an .
alpha.
-hydroxynitrile according to the present invention is not particularly limited as long as the microorganism is capable of producing such an amide or acid from the corresponding



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