Panipenem is a broad-spectrum parenteral carbapenem with activity against aerobic, anaerobic, gram-positive, and gram-negative organisms including non-fermenters. Panipenem is often co-administered with betamipron to prevent nephrotoxicity.
Panipenem/betamipron is a carbapenem antibiotic marketed by Daiichi Sankyo Co. of Japan. It was launched in 1993,[rx] under the brand name Carbenin.[rx]
It is a combination in which panipenem is the carbapenem antibiotic and betamipron inhibits renal uptake of panipenem[rx] and so reduces its nephrotoxicity[rx] (much like the imipenem/cilastatin combination).
The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize a variety of chiral compounds.