GeneORator: a novel and high-throughput method for the synthetic biology-based improvement of any enzyme
Lead Research Organisation:
University of Liverpool
Department Name: Functional and Comparative Genomics
Abstract
Enzymes have significant uses in biotechnology, for instance as components of 'biological' washing powders. The total enzyme market is large, some $8Bn per year.
Natural enzymes are normally very poor. We can improve them by changing their sequences. However, this still scales as powers of their size: for 14 residues the number is greater than the lifetime in s of the known Universe (~100,000,000,000,000,000). We have a new method that allows one to do this additively (for 14 residues it is just 280 examples). This allows us to study the possible variants MUCH more effectively; with one enzyme we have made a variant that is 1210 times quicker than the starting enzyme.
However, we now need to show that this was not a 'fluke' by demonstrating our methods on a series of other enzymes, and, as well as automating our methods using robots, this is what this project will do. This should get us to a state where we can attract sufficient investment to commercial our discoveries properly.
Natural enzymes are normally very poor. We can improve them by changing their sequences. However, this still scales as powers of their size: for 14 residues the number is greater than the lifetime in s of the known Universe (~100,000,000,000,000,000). We have a new method that allows one to do this additively (for 14 residues it is just 280 examples). This allows us to study the possible variants MUCH more effectively; with one enzyme we have made a variant that is 1210 times quicker than the starting enzyme.
However, we now need to show that this was not a 'fluke' by demonstrating our methods on a series of other enzymes, and, as well as automating our methods using robots, this is what this project will do. This should get us to a state where we can attract sufficient investment to commercial our discoveries properly.
Organisations
Publications
Currin A
(2019)
GeneORator: An Effective Strategy for Navigating Protein Sequence Space More Efficiently through Boolean OR-Type DNA Libraries.
in ACS synthetic biology
Doçi G
(2020)
DNA Scanner: a web application for comparing DNA synthesis feasibility, price and turnaround time across vendors
in Synthetic Biology
Hérisson J
(2022)
The automated Galaxy-SynBioCAD pipeline for synthetic biology design and engineering.
in Nature communications
Range J
(2022)
EnzymeML-a data exchange format for biocatalysis and enzymology.
in The FEBS journal
Samanta S
(2020)
VAE-Sim: A Novel Molecular Similarity Measure Based on a Variational Autoencoder.
in Molecules (Basel, Switzerland)
Yeoh J
(2021)
SynBiopython: an open-source software library for Synthetic Biology
in Synthetic Biology
| Description | Autoencoders that use SMILES as inputs can return three kinds of outputs: (i) the correct SMILES output mirroring the input and/or translating into the input molecular structure (referred to as "perfect"), (ii) an incorrect output of a molecule different from the input but that is still legal SMILES (hence will return a valid molecule), referred to as "good", and (iii) a molecule that is simply not legal SMILES. In practice, our VAE after training returned more than 95% valid SMILES in the test (holdout) set, so those that were invalid could simply be filtered out without significant loss of performance. |
| Exploitation Route | This opens up a considerable area of chemical exploration, even in the absence of any knowledge of bioactivities. |
| Sectors | Digital/Communication/Information Technologies (including Software) |
| Title | METHODS FOR PRODUCTION OF ERGOTHIONEINE |
| Description | The present invention relates to microbial factories, in particular yeast factories, for production of ergothioneine. Also provided are methods for producing ergothioneine in a yeast cell, as well as useful nucleic acids, polypeptides, vectors and host cells. |
| IP Reference | WO2020221795 |
| Protection | Patent granted |
| Year Protection Granted | 2020 |
| Licensed | No |
| Impact | The present invention relates to microbial factories, in particular yeast factories, for production of ergothioneine. Also provided are methods for producing ergothioneine in a yeast cell, as well as useful nucleic acids, polypeptides, vectors and host cells. Ergothioneine (ERG) (2-mercaptohistidine trimethylbetaine, (2S)-3-(2-Thioxo-2,3-dihydro-1 H-imidazol-4-yl)-2-(trimethylammonio)propanoate) is a naturally occurring antioxidant that can be found universally in plants and mammals; it possess |
| Description | National TV appearance |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Professor Douglas Kell, Research Chair in Systems Biology was interviewed for UK broadcaster ITV1 and ITVX regarding his research into the health benefits of mushrooms. The interview was part of the programme 'Inside M&S' and pitched at a lay audience. The programme was aired at 9pm on Tuesday, 14 January 2025. |
| Year(s) Of Engagement Activity | 2024 |
| URL | https://tv24.co.uk/b/sq3jo0-dh8 |
| Description | Talk and poster presentation at the Automated Scientist Workshop - The Future of Cell Factory Engineering, 11-15 March 2024 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Talk on 12 March 2024: Machine learning for synthetic biology Navigating sequence space intelligently. Attendance by selected application only. Specialist workshop to share knowledge and ideas, network and collaborate. |
| Year(s) Of Engagement Activity | 2024 |
| URL | https://sciencecluster.dk/event/6966/ |