The optimized biocatalytic synthesis of (S)-methyl 2-chlorobutanoate by Acinetobacter sp. lipase

Chirality. 2022 Sep;34(9):1228-1238. doi: 10.1002/chir.23482. Epub 2022 Jun 17.


Epilepsy is a chronic disease caused by sudden abnormal discharge of brain neurons, leading to transient brain dysfunction. Levetiracetam, developed by the UCB company in Belgium, is an effective drug for the treatment of epilepsy. (S)-Methyl 2-chlorobutanoate is an important chiral building block of levetiracetam, which has attracted a great deal of attention. In this study, a strain of lipase-produced Acinetobacter sp. zjutfet-1 was screened from soil samples. At optimized conditions for fermentation and biocatalysis, the bacterial lipase exhibited high catalytic activity for hydrolysis and stereoselectivity toward racemic methyl 2-chlorobutanoate. When the enzymatic reaction was carried out in 6% of racemic substrate, the enantiomeric excess (e.e.s ) reached more than 95%, with a yield of over 86%. Therefore, this lipase can efficiently resolve racemic methyl 2-chlorobutanoate and obtain (S)-methyl 2-chlorobutanoate, which presents great potential in the industrial production of levetiracetam.

Keywords: (S)-methyl 2-chlorobutanoate; biocatalysis; ester enantioselectivity; levetiracetam; lipase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter* / metabolism
  • Biocatalysis
  • Hydrolysis
  • Levetiracetam
  • Lipase* / metabolism
  • Stereoisomerism


  • Levetiracetam
  • Lipase