Directed Evolution of New Enzymes for Sustainable Chemical Manufacture in Microbial Cells

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Biological Sciences


The creation of new enzymes for the synthesis of drug-like molecules has revolutionised chemical manufacture, especially on the industrial scale.[1] However, despite significant advances in this field in recent years, enzymatic replacements for every organic transformation do not exist. Whilst the sequencing of newly-discovered microorganisms and the analysis of environmental metagenomes will continue to populate the biocatalytic toolbox, it seems unlikely that this approach will ever become a general solution to creating a new biocatalyst for any given organic reaction. The design and re-engineering of existing enzymes to perform novel chemical transformations is therefore an important challenge in organic chemistry.[2]

This project will use directed evolution and a mechanistic knowledge of organic chemistry to create a new family of enzymes capable of catalysing reactions that have (to the best of our knowledge) never existed in Nature. These enzymes will then be used as modular components in designer metabolic pathways to produce small molecules of interest to the pharmaceutical industry directly from renewable resources via microbial fermentation.[3]

The highly multidisciplinary nature of this project will allow the student to develop a strong proficiency in a variety of chemical and biological techniques (e.g. recombinant DNA techniques, PCR, directed evolution, microbiology, in vitro assay development, genome engineering, multistep chemical synthesis and spectroscopic analysis).


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Sadler JC (2021) Interfacing non-enzymatic catalysis with living microorganisms. in RSC chemical biology

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/T517501/1 30/09/2019 29/09/2024
2276108 Studentship EP/T517501/1 01/11/2019 29/04/2024 Nick Johnson
Description Bacteria are increasingly used as a sustainable feedstock of small molecules. By increasing the chemical transformations available to biology, this drastically can increase the scope of products which can be produced biosynthetically. We have identified and developed a reaction in a bacterial cell culture, typically only seen in organic chemistry. By identifying an initial starting substrate, we were able to identify a biocompatible catalyst which was capable of this reaction. This was then further optimised to increase yields. By demonstrating this reaction can be coupled to biological processes, we have initially identified the potential of this reaction being coupled to larger biosynthetic pathways.
Exploitation Route Bacteria can be engineered to synthesise chemicals, chemicals which are used in every day household items. This method can be greener and a more sustainable source of small molecules than typical industrial processes. However, the chemicals which can be synthesised by bacteria is limited to the reactions which occur in Nature. We have been trying to identify and develop non-native reactivity into these living organisms through the use of abiotic catalysis. This could increase the synthetic opportunities provided by biotechnology for the production of value-added compounds from simple sugars or waste feedstocks, creating a more circular economy.
Sectors Chemicals,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology