Bacteria from the Mycobacteriaceae family pose a threat that needs to be tackled. While the rapid expansion of genome sequencing with genome and pathway annotations has greatly improved the progress of drug discovery, it has also pointed out how much our understanding of metabolism is limited. Within the gap of knowledge constituted by genes of unknown or imprecise function are some that encode for metabolic enzymes defining uncharted pathways, potential targets for the development of new fighting methods against those pathogens. Among uncharacterized enzymes that represent exciting opportunities are members of the cytochrome P450 (CYP) protein family. This is because azoles, known CYPs specific inhibitors, have been demonstrated to prohibit M. tuberculosis growth. Logically, CYPs, their required redox partners, and the pathways they are involved in, mostly uncharacterized, have been proposed to be drug targets.
The work carried out for the “deCrYPtion” action consisted in performing a large-scale comparative genomics analysis of the members of the Cytochrome P450 (CYP) protein family present in the genomes of Mycobacterium bacterial species, to propose and then experimentally test functions for some selected targets.
Experimental results obtained regarding the function of previously uncharacterized genes are fundamental in nature. They increase the understanding of pathogens that impact human and animal health. The newly obtained understanding can be leveraged to inform intervention development, i.e. newly obtained knowledge serves the development of new drugs.
At a personal level, the results obtained have been and will be leveraged for the development of proposals aiming at obtaining funding to further the research needed in the context of developing new antitubercular drugs. Research work will continue on the main topic of the deCrYPtion proposal, and it is expected it will lead to publication in international journals.
Dissemination activities:
Open Access data
The scientific information obtained for WP1 and 2 has been made available using the Zenodo open repository and can be accessed at
https://doi.org/10.5281/zenodo.6583999(odnośnik otworzy się w nowym oknie).
Publication
A manuscript describing the comparative genomics approach and its usefulness has been published.
Rémi Zallot, Nils Oberg, John A Gerlt, Discovery of new enzymatic functions and metabolic pathways using genomic enzymology web tools, Current Opinion in Biotechnology, Volume 69, 2021, Pages 77-90, ISSN 0958-1669,
https://doi.org/10.1016/j.copbio.2020.12.004(odnośnik otworzy się w nowym oknie).
(
https://www.sciencedirect.com/science/article/pii/S0958166920301907(odnośnik otworzy się w nowym oknie) and
https://cronfa.swan.ac.uk/Record/cronfa60085(odnośnik otworzy się w nowym oknie))
Invited presentations
Dr Rémi Zallot was invited to present some of work performed during the deCrYPtion action:
- Understanding antimicrobial resistance requires characterising unknown genes identified involved MIB Fellowship days at the Manchester Institute of Biotechnology, The University of Manchester, January 26, 2022
- Similarity Networks (SSNs) and Genome Neighbourhood Networks (GNNs) for function assignment, School of Chemistry, Cardiff University, April 3, 2021
Conference attended (online)
The Microbiology Society: WHY MICROBIOLOGISTS MATTER?
23 – 26 November 2020
Outreach activities
Demonstration of how genomic DNA can be extracted from fruits, allowing to cover what DNA is and to show the public that DNA is something that can be extracted, seen, and worked on by scientists to gain a better understanding of living organisms. The public mostly consisted of a non-scientific audience. The demonstrations were aimed towards families and children.
List of events I was a demonstrator for
- November 2021: St Tydfil’s Old Parish Church, Merthyr Tydfil, in the context of UK Science Festivals Network, Making Connections project grant to Dr. Claire Price.
- July 2021: Merthyr Tydfil Science Festival
- May 2021: Wales Gene Park Genomics Showcase
- February 2021: Cardiff Science Festival
- October 2020: Swansea Science Festival
