Mining extremophile genomes for synthetic biology
Lead Research Organisation:
CARDIFF UNIVERSITY
Department Name: Chemistry
Abstract
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Publications
Blackstock C
(2025)
Nucleic acid joining enzymes: biological functions and synthetic applications beyond DNA.
in The Biochemical journal
| Description | Working in collaboration with Adele Williamson, we have been able to identify, express and purify a novel DNA polymerase from a bacterium that lives in the cold temperatures of the Antarctic. To our delight, this enzyme is capable of making DNA containing non-canonical nucleobases, a key aim of the project, thereby setting the scene for developing a biophysical understanding of its properties. Further advances have been made in terms of metagenomes analysed, consolidating the collaboration. |
| Exploitation Route | If we can engineer the DNA polymerase to have the ability to separate DNA strands in double helices, this enzyme will find numerous commercial applications in diagnostics and other areas of biotechnology. |
| Sectors | Healthcare Pharmaceuticals and Medical Biotechnology |
| Description | A ligase-based solution for non-natural nucleic acid synthesis |
| Amount | $1,000,000 (NZD) |
| Organisation | Ministry of Business, Innovation and Employment |
| Sector | Public |
| Country | New Zealand |
| Start | 09/2022 |
| End | 09/2025 |
| Description | FfAME Collaboration |
| Organisation | Foundation for Applied Molecular Evolution |
| Country | United States |
| Sector | Charity/Non Profit |
| PI Contribution | We have expressed novel psychrophilic DNA polymerases and DNA ligases, and characterized their catalytic activity using DNA oligonucleotides that contain non-canonical nucleobases. These experiments have provided information needed for X-ray crystallography and computational simulations. |
| Collaborator Contribution | Our partners have prepared DNA oligonucleotides that contain non-canonical nucleobases for our biochemical studies. |
| Impact | A review paper (Blackstock et al., [2025] Biochem. J. ) has recently been published, which has been associated with this award. |
| Start Year | 2021 |
| Description | Metagenomic samples from New Zealand geothermal microbiomes (Prof Matthew Stott, School of Biological Sciences, University of Canterbury, New Zealand) |
| Organisation | University of Canterbury NZ |
| Country | New Zealand |
| Sector | Academic/University |
| PI Contribution | Advice and background information for selection of biotechnologically-relevant enzymes from these metagenomes. |
| Collaborator Contribution | Access to metagenomic sample sequences for use in the project. These are in the process of being analysed by the team members involved in this collaboration. |
| Impact | Output (scientific peer-reviewed paper) in progress. |
| Start Year | 2022 |
| Description | Wakaito Unversity |
| Organisation | University of Waikato |
| Country | New Zealand |
| Sector | Academic/University |
| PI Contribution | We have expressed and characterized novel DNA polymerases from psychrophilic bacteria. More recently, we have performed molecular dynamics (MD) simulations to understand the observed activity of DNA ligases with nicked DNA containing non-canonical nucleobases. |
| Collaborator Contribution | Our partners have provided gene sequence information on the DNA polymerases that are present in "dry valley" bacteria, which live at low temperatures in the Antarctic. They have also provided new X-ray crystal structures in which DNA ligases are complexed with nicked DNA containing non-canonical nucleobases, which are the basis of our computational models, together with assay data. |
| Impact | A review paper (Blackstock et al., Biochem. J. 2025) has recently been published, which has been associated with this award. |
| Start Year | 2021 |
| Description | Journal Editor - Philosophical Transactions B |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I was the lead Editor for a special issue the Philosophical Transactions of the Royal Society B titled "Reactivity and Mechanism in Chemical and Synthetic Biology". This was a collection of articles by leading international practitioners in the fields of chemical biology and synthetic biology. |
| Year(s) Of Engagement Activity | 2023 |