New Metabolic Chemistry for Biocompatible Reactions

The field of engineering biology aims to create new metabolic pathways to access chemical products from sustainable feedstocks via fermentation. However, metabolic chemistry is limited to reactions that have evolved in Nature and remains dwarfed by the chemical diversity accessible from petrochemicals by synthetic organic chemists. Urgent solutions must now be sought to bridge this gap and enable the transition of the chemical industry to a more sustainable, climate-positive and net-zero future. Over the past 8 years I have led the emerging field of biocompatible chemistry, which addresses this challenge by interfacing non-enzymatic reactions with metabolism to expand cellular chemistry. This ambitious research has broken boundaries at the interface of chemical catalysis and metabolic engineering, yet the full transformative potential of biocompatible chemistry has still to be realised, and two key fundamental questions remain unanswered: can biocompatible chemistry be fully integrated with cellular metabolism and what are the rules governing biocompatibility? To answer these questions, MICROCHEMIST and my ERC-CoG team will achieve a step-change in what is possible in this emerging field by interfacing chemo-catalysts with the metabolic function of new microorganisms and within new ambitious metabolic designs. This will open up entirely new directions of travel for biocompatible chemistry by (i) harnessing new metabolic chemistry (ii) interfacing multiple metabolic pathways simultaneously, (iii) uncovering the fundamental rules for biocompatible reaction success, and for the first time (iv) fully integrating non-enzymatic reactions within metabolism to create new metabolic products. This unique and highly multidisciplinary approach will revolutionise the fields of both chemical and biological synthesis and accelerate the transition towards a greener and more sustainable chemical industry.