Active Chemistry Cells, Biochemistry & Physiology

Non-Enzymatic Catalysis in the Microbial Cell Interior

In plain English

AI plain-English summary

Plastic bottles, polyester clothing, and many medicines start as crude oil, but a new project aims to grow them inside living microbes instead. The problem is that microorganisms can only make molecules that evolution has already invented, leaving out the vast range of "non-natural" chemicals needed for everyday products. Project MICROCAT is developing synthetic catalysts—small chemical tools that work inside living cells—to perform reactions that nature never evolved. These catalysts will be transported into microbes and linked to the cells' own metabolism, creating hybrid systems that churn out new-to-nature compounds. If it works, the chemical industry could shift from drilling for fossil feedstocks to fermenting sustainable sugars in bioreactors, cutting carbon emissions without redesigning the products themselves. This is fundamental science: no immediate consumer gadget or drug will emerge from this grant. But past work in synthetic biology has already turned microbes into factories for insulin and artemisinin, and this project aims to unlock a much wider chemical palette for the same approach.

View original technical description
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.

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Researchers

Stephen Wallace (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

New Metabolic Chemistry for Biocompatible Reactions
Directed Evolution of New Enzymes for Sustainable Chemical Manufacture in Microbial Cells
Engineering the convergence of chemistry and biology: resolving the incompatibility of bio- and chemical catalysis
Design and Evolution of Enzymes with Non-Canonical Amino Acids
Development of chemo-biocatalytic cascades for industrial synthesis

Original classification

Fellowship

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