EASTBIO Exploring the Untapped Chemical Potential of the Microbial World – a cellular and synthetic biology approach to organic synthesis

Synthetic biology is revolutionising the field of chemical synthesis. Using genetically modified microorganisms this approach enables the production of compounds of industrial importance (e.g. pharmaceuticals, agrochemicals, materials, cosmetics, etc.) directly from renewable feedstocks (e.g. sugar, CO2, methane) via fermentation.
Inherent to this approach is the ability to transfer and assemble genes from various sources (e.g. plants, reptiles and bacteria) together in one cell to build new “designer” biosynthetic pathways. However, despite the success of this approach, the inherent chemical capabilities of native microorganisms have received comparatively little attention.

The Project:
This project will examine the chemistry of a variety of microorganisms and use these cells to synthesise a range of target compounds relevant to the pharmaceutical industry. We will focus our attention on microorganisms isolated from extreme environments (e.g. volcanic soil, hydrothermal vents, sub-aquatic regions, and sites of meteor impact – so-called “extremophiles”. Using an in-house focussed library of organic compounds, we will assess the functional group transformations that can be achieved by these organisms under a range of reaction conditions. Successful reactions will be optimised using standard microbiology techniques and, where possible, improved further using synthetic biology tools (e.g. metabolic engineering, CRISPR-Cas). Finally, these new biotransformations will be applied to the synthesis of a pharmaceutically-relevant target compound through our existing links with industry.

Training Environment:
The multi-disciplinary nature of this project will allow students to develop a strong proficiency in synthetic biology techniques, microbiology, whole-cell biocatalysis and organic synthesis. This will include experience in a range of chemical and bio-analytical techniques, such as 1-/2D-NMR, mass spectrometry, HPLC, GC, LC-MS, DNA sequencing, colony PCR and gel electrophoresis. As such, this project will likely be best suited to students from a chemistry and/or biology background with an interest in biocatalysis, synthetic biology, green chemistry and industrial biotechnology.

The use of microbial cells for chemical synthesis is an exciting new area of research. A PhD in this area will equip the student with a broad set of modern experimental and analytical techniques in chemistry and biology that will be highly relevant for a future career in academia or industry. More information on this area of research can be found in our lab’s recent publications [1,2].

This project will be co-supervised by Dr Stephen Wallace at the Institute of Quantitative Biology, Biochemistry and Biotechnology (IQB3) and Dr Annamaria Lillienkampf in the School of Chemistry at the University of Edinburgh.