Adaptation of Enzymes Involved in the Valine Pathway for the Production of Methacrylate Intermediates
Lead Research Organisation:
University of Aberdeen
Department Name: Chemistry
Abstract
Methacrylate (MA) is an organic compound and is produced industrially on a large scale as a precursor. Over three million tons of MA are produced annually. MAs have numerous applications, including the manufacture of the acrylate polymers with trade names such as Lucite and Plexiglas. They can also be used as the monomer resin in windscreen repair kits, bone cement for fixing prosthetic devices in orthopaedic surgery. Currently MAs are mainly prepared synthetically by using toxic chemical agents, such as the extremely hazardous substance acetone cyanohydrin and sulphuric acids. Therefore, there is an undiminishing need to allow a safer and greener synthetic strategy in industry, particularly under mild conditions. In this respect, microbial fermentation and synthetic biology approaches to produce MAs or derivatives is an attractive option. In this project, we are aiming at manipulating key enzymes in the biosynthetic pathway of L-valine, the important primary metabolism to produce MA intermediate which can be readily converted into MA under mild conditions.
The project directly addresses the industrial needs and will allow the PhD student to be immersed with a multidisciplinary training, including chemical synthesis, enzymology, molecular biology, synthetic biology, biotransformation and industrial biotechnology.
The project directly addresses the industrial needs and will allow the PhD student to be immersed with a multidisciplinary training, including chemical synthesis, enzymology, molecular biology, synthetic biology, biotransformation and industrial biotechnology.
| Description | -One of the milestones of my projects were to chemically synthesize a molecule that I would later use. This synthesis was performed following the procedure of a patent that lacked a lot of information, so with the synthesis I performed I made the procedure in the patent much more clear and could be used by anyone in the future. - Another milestone involved mutating key parts of the enzyme I am working with by a technique called Site Directed Mutagenesis, that allowed to understand which parts of the wild type enzymes are key for it to function normally. - The third milestone is to couple all the parts of a complex "puzzle" I have been working on for the last half a year. |
| Exploitation Route | - The overall synthesis procedure has been completely detailed, so other researchers could perfectly carry the synthesis out with the details I added to it. - With the Site Directed Mutagenesis experiment, more information about how the enzyme works has been studied and this information can be used for further studies. - When the third milestone will be fully completed, this complex coupled structure could be used with industrial purposes. |
| Sectors | Chemicals,Environment,Manufacturing, including Industrial Biotechology |
| Title | Chemical synthesis procedure |
| Description | The only published patent related to a compound I needed to synthesize lacked a lot of information in order to perform the chemical synthesis of the compound. What I did, was to add all the necessary details so that the chemical synthesis could be carried out. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2019 |
| Provided To Others? | No |
| Impact | With this improved procedure, anyone could easily perform the synthesis of the compound I synthesized. |
| Title | Coupled enzymatic reaction assay developments |
| Description | I took existing bacterial metabolic pathways, modified and coupled them to other enzymatic reactions for a specific purpose. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2021 |
| Provided To Others? | No |
| Impact | This development will help the overall objective of my project to be fulfilled. |
| Title | Developed synthetic plasmids |
| Description | Synthetic plasmids were designed in order to express a very specific type of gene for a very specific type of protein obtainment. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2019 |
| Provided To Others? | No |
| Impact | Designed synthetic plasmids can be used by anyone that need to express the gene and protein the plasmid secquence codes for. |
| Title | Mutated proteins for enzymatic studies |
| Description | I isolated a wild type enzyme and then mutated them. I managed to isolate the mutants developing a full detailed procedure and made several experiments with the mutated proteins. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2019 |
| Provided To Others? | No |
| Impact | With the protocol I developed and the enzymes I isolated, some researchers could easily follow the procedure to use these kind of mutated enzymes. |
| Description | Information and material exchange |
| Organisation | Ingenza Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | The project is run between the University of Aberdeen and Ingenza Ltd. Most of the work is run at the University. We have meetings several times per year in which updates are discussed and at some points material transfer agreements have been developed. |
| Collaborator Contribution | Ingenza Ltd. has a big expertise in synthetic and evolutionary biology so they have provided us with some materials that we can not develop at the University facilities. Their expertise has helped the project to continue working. Will benefit from a placement in this institution to learn how an industry works and will be able to use the different techniques they posses. |
| Impact | Information and material exchange |
| Start Year | 2017 |
| Description | Lucite |
| Organisation | Lucite International |
| Department | Lucite International UK Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Lucite International is the leading company that manufacture methylcrylate chemicals. The R&D department has been interested in the above research and invited us to join its consortium of bio-based methylcrylate manufacturing. The student, PI and CoI participated the consortial meetings in 2019 and 2020. We have also had a 6-month review meeting since 2019. |
| Collaborator Contribution | The partnership brought the expertise in the bio-based methylcrylate manufacturing. the industrial partners provided key suggestions/guidance related to industrial setting which are valuable for us to make further progress of the project. |
| Impact | it is multi-displinary. we signed a confidential contract with Lucite to participate the consortial meetings. |
| Start Year | 2019 |
| Description | Talking to school students across the UK as a scientist about science related questions they have |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | "I'm a scientist,get me out of here" is an activity where scientists and school students connect online and they can ask all the questions that they want. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://imascientist.org.uk/ |
| Description | Connect with school students and answer what they always wanted to ask a scientist |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | I'm a Scientist is an online, student-led STEM enrichment activity. It connects school students with scientists through real-time text based chats. Students can ask anything they want about my daily work, my background, my skills etc. This way they get a closer view about what a STEM job is and they get the chance to ask actual scientist everything they have always wanted to ask them. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Event for Public Engagement developing an activity that explains the key points of our project |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | We spent three days learning how to communicate our projects to people with no science background with an activity we created. We stood in the street to talk to people about our projects and the local newspaper covered the event. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.obantimes.co.uk/2018/07/31/the-future-of-our-seas/ |
| Description | Inspire young girls (11-16 years old) into STEM |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | The Martin High School was looking for women in STEM roles, to help inspire the girls of their school. They wanted women in stem careers to record themselves talking about their job, involving our role and career sector, any advice for young girls considering entering into this career. They also wanted us to tell all the experiences we have faced as a woman in our role and which barriers we have broken down to get where we are. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Presented and won a poster competition at IBioIC 6th Annual Conference in Glasgow |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Industry/Business |
| Results and Impact | I had the opportunity to present a poster in a Biotechnology Conference in Glasgow in which the creativity was awarded. The further of the classical type of conference poster, the more chances you had to win a prize. A lot of people approached me to see my poster and I was lucky that people really liked my poster and therefore, I won the prize. |
| Year(s) Of Engagement Activity | 2020 |
| Description | RSC Perkin conference attendance and poster presentation |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Industry/Business |
| Results and Impact | I had the chance to present a poster at the Royal Society of Chemistry Perkin conference in which I could explain the latest experiments I have performed during these two years of research |
| Year(s) Of Engagement Activity | 2020 |
| Description | SMF Aspiring Professionals programme volunteer |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | This mentoring programme was created in order to provide opportunities, and networks of support for 16-17 year olds who are unable to get them from their schools or families. I was matched with a 16 year old girl that wanted to study a STEM related degree and I mentored her all the way through her decision taking, university choosing, university application and university interviews. |
| Year(s) Of Engagement Activity | 2020 |
| Description | School visit |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | St Joseph Primary School organised "Science Day" June, 2019 and invited HD to participate in this event. HD briefly introduced the principles of biochemistry and presented a colorimetric experiment including a series of enzymatic reactions to aspire school pupiles and general audience. The teachers told HD that it appeared that there have been increased interest in the school in biochemistry/chemistry. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Talk at Lucite Biotechnology Symposium about my project to the experts on the field |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Industry/Business |
| Results and Impact | The project I am carrying out has some industrial collaborators, so from time to time, they organize a symposium and the PhD students and PI have the chance to explain what we have done and what we will be doing and get some feedback. In this occasion, I could talk about my project for 30 minutes. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Talk to Mitsubishi Japan collaborators about my project |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | My project has some industrial collaborators including Mitsubishi. last year I had the chance to explain what I had done so far to people coming from Mitsubishi Japan, get feedback from them and they told be about how such a big company works. |
| Year(s) Of Engagement Activity | 2019 |