De Novo Enzyme Cascades in Whole Cells for the Synthesis of Chiral Cyclic Amines.

Research output: Contribution to journalArticle

  • External authors:
  • Lorna Hepworth
  • Scott France
  • Shahed Hussain
  • Peter Both

Abstract

The increasing diversity of reactions mediated by biocatalysts has led to development of multi-step in vitro enzyme cascades, taking advantage of generally compatible reaction conditions. The construction of pathways within single whole cell systems is much less explored, yet has many advantages. Herein we report the generation of a successful whole cell de novo enzyme cascade for the diastereoselective and/or enantioselective conversion of simple, linear keto acids into valuable cyclic amine products. The pathway starts with carboxylic acid reduction that triggers a transamination, imine formation and subsequent imine reduction. Construction and optimization of the system was achieved by standard genetic manipulation and the cascade required only starting material, amine donor and whole cell catalyst with cofactors provided internally by glucose metabolism. A panel of synthetic keto acids provided access to piperidines in high conversions (up to 93%) and ee (up to 93%).

Bibliographical metadata

Original languageEnglish
JournalACS Catalysis
Early online date14 Mar 2017
DOIs
StatePublished - 2017