Visiting Speaker:? Sabine L. Flitsch, Professor of Chemical Biology, University of Manchester
The combination of sequential biocatalytic reactions in non-natural synthetic cascades is a rapidly developing field and leads to the generation of complex valuable chemicals from simple precursors. As the toolbox of available biocatalysts continues to expand, so do the options for biocatalytic retrosynthesis of a target molecule, leading to new routes employing enzymatic transformations. The implementation of such cascade reactions requires careful consideration, particularly with respect to whether the pathway is constructed in vitro or in vivo. This lecture will showcase three successful de novo cascades and discuss the relative merits of in vitro, in vivo or hybrid approaches to building biocatalytic cascades and analytical challenges. Biocatalysts were obtained either directly from genomic libraries, by re-design of enzyme activity to suit required substrate specificity and selectivity or by exploiting enzyme promiscuity. A particularly important reaction class for enzyme cascades is C-H activation, which allows for the stereoselective functionalisation of simple organic substrates and biological feedstocks, such as fatty acids.
References: ACIE 2020, 132, 1; ChemCatChem 2018, 10, 1042; ACS Catalysis 2017, 7, 710; ACS Catalysis 2017, 7, 2920; JACS 2017, 139, 1408; ACIE 2017, 56, 1; ACIE 2017, 56, 14498; Nature Comm 2017, 8, 973; ACIE 2016, 55, 1511; Nature Chemistry 2014, 6, 65; JACS 2012, 134, 4521.
Sabine has a long-standing interest in the application of biocatalysis to organic synthesis. More recently, she has developed multistep cascade reactions mediated by enzymes, both in cell free and whole cell systems for the stereoselective synthesis of carbohydrates and amines.
Sabine obtained a Diploma in Chemistry from the University of Muenster, Germany and a DPhil degree from Oxford University under the supervision of Sir J E Baldwin. She spent three years of postdoctoral studies with Professor H G Khorana at MIT before returning to the UK to pursue her academic career at the Universities of Exeter, Oxford, Edinburgh and now Manchester, where she has held a Chair since 2004.