Synthesis of ethyl-(3 R,5 S)-dihydroxy-6-benzyloxyhexanoates via diastereo- and enantioselective microbial reduction: Cloning and expression of ketoreductase III from Acinetobacter sp. SC 13874

• Published in: Enzyme and microbial technology Vol. 43; no. 7; pp. 544 - 549
• Main Authors: Goldberg, Steven, Guo, Zhiwei, Chen, Steve, Goswami, Animesh, Patel, Ramesh N.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 10.12.2008; Elsevier
• Subjects: Acinetobacter; Biocatalysis; Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; Cloning and expression; Enantioselective diastereoselective reduction; Escherichia coli; Fundamental and applied biological sciences. Psychology; Ketoreductase; Methods. Procedures. Technologies; Ketoreductase; Cloning and expression; Enantioselective diastereoselective reduction; Biocatalysis; Reduction; Enantioselectivity; Neisseriaceae; Bacteria; Micrococcales; Acinetobacter; Microorganism
• ISSN: 0141-0229; 1879-0909
• DOI: 10.1016/j.enzmictec.2008.07.005

Previously we have demonstrated the reduction of ethyl and t-butyl diketoesters 1 to the corresponding syn-(3 R,5 S)-dihydroxy esters 2a by Acinetobacter sp. 13874. The syn-(3 R,5 S)-dihydroxy ester 2a was obtained with an enantiomeric excess (e.e.) of 99% and a diastereomeric excess (de) of 63%. In this report, we identified a gene encoding desired ketoreductase III which catalyzed the diastereoselective reduction of diketoesters 1 to syn-(3 R,5 S)-dihydroxy esters 2a and describe cloning and expression of ketoreductase III into Escherichia coli. Cells or extracts of recombinant E. coli efficiently reduced the diketoester 1 to the corresponding syn-(3 R,5 S)-dihydroxy ester 2a in 99.3% yield, 100% e.e., and 99.8% de.