Stereoselective preparation of lipidated carboxymethyl-proline/pipecolic acid derivatives via coupling of engineered crotonases with an alkylmalonyl-CoA synthetase

Org Biomol Chem. 2013 Dec 21;11(47):8191-6. doi: 10.1039/c3ob41525b. Epub 2013 Oct 9.

Abstract

The trisubstituted enolate- and C-C bond-forming capacities of engineered carboxymethylproline synthases CMPSs are coupled with the malonyl-CoA synthetase MatB to enable stereoselective preparation of 5- and 6-membered N-heterocycles functionalised with alkyl-substituted carboxymethyl side chains, starting from achiral alkyl-substituted malonic acids and L-amino acid semialdehydes. The results illustrate the biocatalytic utility of crotonases in tandem enzyme-catalysed reactions for stereoselective synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Biocatalysis
  • Coenzyme A Ligases / chemistry
  • Coenzyme A Ligases / metabolism*
  • Enoyl-CoA Hydratase / chemistry
  • Enoyl-CoA Hydratase / metabolism*
  • Lipids / chemistry*
  • Models, Molecular
  • Molecular Structure
  • Pipecolic Acids / chemistry
  • Pipecolic Acids / metabolism*
  • Proline / biosynthesis*
  • Proline / chemistry
  • Protein Engineering*
  • Stereoisomerism

Substances

  • Bacterial Proteins
  • Lipids
  • Pipecolic Acids
  • Proline
  • Enoyl-CoA Hydratase
  • Coenzyme A Ligases
  • malonyl-CoA synthetase
  • pipecolic acid