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Extended Reaction Scope of Thiamine Diphosphate Dependent Cyclohexane‐1,2‐dione Hydrolase: From CC Bond Cleavage to CC Bond Ligation
Author(s) -
Loschonsky Sabrina,
Wacker Tobias,
Waltzer Simon,
Giovannini Pier Paolo,
McLeish Michael J.,
Andrade Susana L. A.,
Müller Michael
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201408287
Subject(s) - chemistry , bond cleavage , aldehyde , cyclohexane , stereochemistry , cyclohexanone , thiamine , ketone , medicinal chemistry , catalysis , organic chemistry
ThDP‐dependent cyclohexane‐1,2‐dione hydrolase (CDH) catalyzes the CC bond cleavage of cyclohexane‐1,2‐dione to 6‐oxohexanoate, and the asymmetric benzoin condensation between benzaldehyde and pyruvate. One of the two reactivities of CDH was selectively knocked down by mutation experiments. CDH‐H28A is much less able to catalyze the CC bond formation, while the ability for CC bond cleavage is still intact. The double variant CDH‐H28A/N484A shows the opposite behavior and catalyzes the addition of pyruvate to cyclohexane‐1,2‐dione, resulting in the formation of a tertiary alcohol. Several acyloins of tertiary alcohols are formed with 54–94 % enantiomeric excess. In addition to pyruvate, methyl pyruvate and butane‐2,3‐dione are alternative donor substrates for CC bond formation. Thus, the very rare aldehyde–ketone cross‐benzoin reaction has been solved by design of an enzyme variant.