Efficient bioreduction of bicyclo[2.2.2]octane-2,5-dione and bicyclo[2.2.2]oct-7-ene-2,5-dione by genetically engineered Saccharomyces cerevisiae.
A screening of non-conventional yeast species and several Saccharomyces cerevisiae (baker's yeast) strains overexpressing known carbonyl reductases revealed the S. cerevisiae reductase encoded by YMR226c as highly efficient for the reduction of the diketones 1 and 2 to their corresponding hydroxyketones 3-6 (Scheme 1) in excellent enantiomeric excesses. Bioreduction of 1 using the genetically engineered yeast TMB4100, overexpressing YMR226c, resulted in >99% ee for hydroxyketone (+)-4 and 84-98% ee for (-)-3, depending on the degree of conversion. Baker's yeast reduction of diketone 2 resulted in >98% ee for the hydroxyketones (+)-5 and (+)-6. However, TMB4100 led to significantly higher conversion rates (over 40 fold faster) and also a minor improvement of the enantiomeric excesses (>99%).
Friberg
Annika
A
Division of Organic Chemistry, Center for Chemistry and Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund, Sweden.
Johanson
Ted
T
Franzén
Johan
J
Gorwa-Grauslund
Marie F
MF
Frejd
Torbjörn
T
D001643:Bridged Bicyclo Compounds / Q000737:chemistry / Q000378:metabolism*; D005818:Genetic Engineering / Q000379:methods; D007659:Ketones / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*
D001643:Bridged Bicyclo Compounds; D007659:Ketones; C521607:bicyclo(2.2.2)octane-2,5-dione; D010088:Oxidoreductases