Non-Enzymatic Catalysis in the Microbial Cell Interior

The field of synthetic biology enables industrial chemicals that are currently derived from unsustainable fossil fuels to instead be manufactured from sustainable feedstocks by living microorganisms. However, the diversity of chemicals that can be accessed via this approach is currently limited to molecules that have evolved in nature. Accessing 'non-natural' chemicals that we need to manufacture our clothing, medicines and many other every-day products is a current limitation of this emerging new technology.

Project MICROCAT aims to address this limitation by developing biocompatible chemical catalysts that can perform non-natural reactions under bio-relevant conditions, and then be transported inside of microorganisms and interfaced with metabolism to enable the biosynthesis of new-to-nature compounds in living cells. This new approach will rapidly increase the range of products that can be bio-manufactured in the future and will simultaneously contribute to defossilizing the chemical industry towards net-zero.

To achieve this, project MICROCAT is working on three main objectives: (i) The intracellular transport and activity of chemo-catalysts within lipid droplet producing microorganisms. (ii) Fully integrating biocompatible reactions with cellular metabolism to create self-propagating metabolic circuits.

(iii) The scale-up of chemo-enzymatic processes in engineered microorganisms.

During Phase 1 of this Future Leaders Fellowship, various new biocompatible reactions were discovered and shown to react cooperatively with native and engineered microbial metabolism. During Phase2, these concepts will be extended to include the use of catalytically active transition metal catalysts within living cells, within active metabolic pathways, and within large-scale bioreactors.