Unifying Scheme for the Biosynthesis of Acyl-Branched Sugars: Extended Substrate Scope of Thiamine-Dependent Enzymes

Jan Patrick Steitz, Leonhard Krug, Lydia Walter, Karel Hernández, Caroline Röhr, Pere Clapés, Michael Müller

Research output: Indexed journal article Articlepeer-review

7 Citations (Web of Science)

Abstract

Thiamine diphosphate (ThDP) dependent enzymes are useful catalysts for asymmetric C−C bond formation through benzoin-type condensation reactions that result in α-hydroxy ketones. A wide range of aldehydes and ketones can be used as acceptor substrates; however, the donor substrate range is mostly limited to achiral α-keto acids and simple aldehydes. By using a unifying retro-biosynthetic approach towards acyl-branched sugars, we identified a subclass of (myco)bacterial ThDP-dependent enzymes with a greatly extended donor substrate range, namely functionalized chiral α-keto acids with a chain length from C4 to C8. Highly enantioenriched acyloin products were obtained in good to high yields and several reactions were performed on a preparative scale. The newly introduced functionalized α-keto acids, accessible by known aldolase-catalyzed transformations, substantially broaden the donor substrate range of ThDP-dependent enzymes, thus enabling a more general use of these already valuable catalysts.

Original languageEnglish
Article numbere202113405
Number of pages5
JournalAngewandte Chemie - International Edition
Volume61
Issue number12
DOIs
Publication statusPublished - 14 Mar 2022
Externally publishedYes

Keywords

  • Aasymmetric synthesis
  • Biocatalysis
  • Biogenesis
  • Carboligation
  • Lipopolysaccharides

Fingerprint

Dive into the research topics of 'Unifying Scheme for the Biosynthesis of Acyl-Branched Sugars: Extended Substrate Scope of Thiamine-Dependent Enzymes'. Together they form a unique fingerprint.

Cite this