Microbial reduction of alpha-chloroketone to alpha-chlorohydrin.
Microbial reduction of alpha-chloroketone to alpha-chlorohydrin was studied as one of the approaches for construction of the chiral center of the corresponding epoxide. About 100 microorganisms covering many species of Candida, Pichia, Hansenula, Geotrichum, Rhodococcus and Aureobasidium were screened to reduce the alpha-chloroketone stereospecifically. Many strains provided the R-alpha-chlorohydrin with 100% enantiomeric excess (ee), e.g., Candida sonorensis SC 16117, Geotrichum candidum SC 5469, Rhodotorula glutinis SC 16293, Sphingomonas paucimobilis SC 16113, Pichia silvicola SC 16159 and Rhodococcus equi SC 15835. Few microorganisms showed preferential formation of S-alpha-chlorohydrin after reduction. Among them, Pichia pinus SC 13864 and two Pichia methanolica strains SC 16116 and SC 13860 were the best, providing the S-alpha-chlorohydrin with ee of 88%, 79% and 78%, respectively. The enantiospecificity of the reduction by these Pichia species can be modified by changing the pH or prior heat treatment of the cells and S-alpha-chlorohydrin with > or =95% ee was obtained by appropriate modification of reaction conditions.
Goswami
A
A
Process Research and Development, Bristol-Myers Squibb Pharmaceutical Research Institute, New Brunswick, NJ 08903, USA.
Mirfakhrae
K D
KD
Totleben
M J
MJ
Swaminathan
S
S
Patel
R N
RN
D001419:Bacteria / Q000378:metabolism*; D001711:Biotransformation; D005658:Fungi / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007982:Levulinic Acids / Q000378:metabolism*; D010084:Oxidation-Reduction; D010843:Pichia / Q000378:metabolism; D000517:alpha-Chlorohydrin / Q000378:metabolism*
D007982:Levulinic Acids; C021959:2-amino-4-oxo-5-chloropentanoate; D000517:alpha-Chlorohydrin