10.1021/acscatal.7b00513.s001 Lorna J. Hepworth Lorna J. Hepworth Scott P. France Scott P. France Shahed Hussain Shahed Hussain Peter Both Peter Both Nicholas J. Turner Nicholas J. Turner Sabine L. Flitsch Sabine L. Flitsch Enzyme Cascades in Whole Cells for the Synthesis of Chiral Cyclic Amines American Chemical Society 2017 imine Chiral Cyclic Amines keto acids carboxylic acid reduction cyclic amine products enzyme pathway conversion cascade 2017-03-14 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Enzyme_Cascades_in_Whole_Cells_for_the_Synthesis_of_Chiral_Cyclic_Amines/4793620 The increasing diversity of reactions mediated by biocatalysts has led to development of multistep 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 enantiomeric excess (up to 93%).