Get access

Elucidation of the Enantioselective Cyclohexane-1,2-dione Hydrolase Catalyzed Formation of (S)-Acetoin

Authors

  • Sabrina Loschonsky,

    1. Institute of Pharmaceutical Sciences, University of Freiburg, Albertstraße 25, 79104 Freiburg (Germany), Fax: (+49) 761-203-6351
    Search for more papers by this author
  • Simon Waltzer,

    1. Institute of Pharmaceutical Sciences, University of Freiburg, Albertstraße 25, 79104 Freiburg (Germany), Fax: (+49) 761-203-6351
    Search for more papers by this author
  • Volker Brecht,

    1. Institute of Pharmaceutical Sciences, University of Freiburg, Albertstraße 25, 79104 Freiburg (Germany), Fax: (+49) 761-203-6351
    Search for more papers by this author
  • Prof. Dr. Michael Müller

    Corresponding author
    1. Institute of Pharmaceutical Sciences, University of Freiburg, Albertstraße 25, 79104 Freiburg (Germany), Fax: (+49) 761-203-6351
    • Institute of Pharmaceutical Sciences, University of Freiburg, Albertstraße 25, 79104 Freiburg (Germany), Fax: (+49) 761-203-6351

    Search for more papers by this author

Abstract

Thiamine diphosphate (ThDP) dependent enzymes catalyze the formation of acetoin (3-hydroxybutan-2-one) through one of three different pathways: homocoupling of pyruvate, homocoupling of acetaldehyde, or cross-coupling of acetaldehyde (as acceptor) and pyruvate (as donor). The enantioselectivity of the resulting acetoin is highly dependent on the particular enzyme. We established that ThDP-dependent cyclohexane-1,2-dione hydrolase (CDH) is able to form (S)-acetoin with particularly high enantioselectivity (up to 95 % ee) by all three pathways. Mechanistic studies utilizing 13C-labeled substrates revealed an unprecedented non-acetolactate pathway for the homocoupling of pyruvate, which explains the high enantioselectivity in the CDH-catalyzed formation of (S)-acetoin.

Ancillary