Maximising Metabolic Efficiency for Cellular Alkyl Methacrylate Production

Methyl Methacrylate (MMA) is the monomer for "Perspex" generation. Lucite International is a global chemical company supplying approximately one third of the total MMA market today. Lucite's management have set the vision to develop a wholly sustainable methacrylate manufacturing processes, with utilisation of sustainable biobased feedstocks, to displace current fossil carbon feedstock processes. This is driven both by a market demand, with several customers requesting biobased and by the long term aim to reduce carbon dioxide emissions and contribute to the efforts to reduce global warming.
Lucite has worked on this problem for several years with both other industrial and academic partners. The principle hurdle has been the requirement to develop a biobased process that can compete economically with petrochemical-based processes. Whilst customers want biobased MMA, it is clear that they will not pay a significant premium, if any. This project builds on significant process engineering work carried out by Lucite on several options to produce biobased methacrylate esters. We now believe in this project we can develop a technology that can compete on a cost per tonne basis with petrochemical-produced methacrylates. The key drivers are the efficient utilisation of lignocellulosic feedstock (both C5 and C6 monosaccharides) and the minimisation of downstream processing costs.
Lucite and its partners, both in industry and academia, are building the first-generation alkyl methacrylate microbial production system in order to realise this vision. The programme is delivering a new bioprocess to alkyl methacrylates from renewable lignocellulosic feedstocks. Lucite and its partners have delivered engineered strains able to convert simple carbohydrate feedstock to an alkyl methacrylate. This project specifically focuses on using a synthetic biology approach to advance the technology to achieve a strain capable of carbon-efficient conversion of D-xylose and glucose to alkyl methacrylates, by redox balancing to reduce carbon loss as carbon dioxide. The scope of work detailed in this application is highly innovative and demonstrates the wider consideration towards full sustainability and carbon reduction for IB chemical manufacturing. Using a synthetic biology approach to activate pathways of choice in the producer strain we shall demonstrate improved carbon conversion efficiencies towards biobased alkyl methacrylates from lignocellulosic wastes. The new routes convert C5/C6 sugars directly to TCA cycle intermediates, and on to chemical products, providing significantly improved atom economy over existing strategies. The developed strains will be eventually put into commercial production by Lucite for sustainable bio-based methacrylate esters production.

The global market for methacrylate production is $8Bn and expected to grow to $11Bn by 2022. Current industrial routes to methacrylates operate under harsh synthetic chemistry conditions and there is demand for a greener more cost-efficient route. No biobased route for industrial production of methacrylates has been developed yet. Current approaches under development suffer from redox imbalance and require delivery of oxygen to the fermentation medium. Higher oxygen demand correlates with higher sugar feedstock consumption, higher generation of heat within the fermenter and eventually impacts the commerciality of the process. Using synthetic biology, we will rationally engineer a bacterial strain capable of utilizing simple carbohydrates (D-xylose and glucose) from lignocellulosic wastes to produce alkyl methacrylate. To overcome the redox imbalance issue and maximize metabolic efficiency, we seek to deploy three concerted pathways for the convergent biosynthesis of methacrylate esters, and minimise the oxygen requirement. The project will not only deliver enhanced carbon conversion efficiency from D-xylose/glucose to product, lessening carbon dioxide waste, but will also assist in establishing a route that is more energy and cost efficient. Key enzymes within the three targeted pathways have been identified (including using modern (structural) bioinformatic approaches) and tested for successful catalysis of the transformations of interest.
Whilst use of the proposed maximisation of the metabolic efficiency for cellular methacrylate production as described in this application is not in itself required to achieve biobased methacrylate production, without its incorporation, the likelihood of commercial investment to full manufacturing scale is increasingly difficult to rationalise.

The technology being developed within this proposal focuses on maximising the usage rate of simple carbohydrate input (derived from lignocellulosic feedstock) to a fermentation process towards generating saleable product, alkyl methacrylate. Methacrylate-based materials play an important part in public quality of life, being found in a wide range of consumer products and electronics, whilst its biocompatibility ensures a growing market for medical/healthcare devices. Fluctuations in oil prices have already impacted on cost of goods, and sustainable, bio-derived alkyl methacrylates will lead to a more stable price structure. Stable prices will also accelerate introduction of new or improved products for consumers or reversion to methacrylate-based products where lower performance, alternative materials have supplanted methacrylates. Most importantly, sustainable manufacturing will deliver environmental benefits, including alternatives to increasingly damaging oil and gas extraction technology, and reduced greenhouse gas emission, mitigating climate change and enabling companies to anticipate future government legislation on sustainability.
This technology being developed can potentially abate carbon dioxide that would otherwise be generated, lessening environmentally damaging carbon dioxide output from biobased manufacturing of alkyl methacrylates.
Lucite are already supplying and have customers in place ready and willing to purchase biobased methacrylate. Whilst there is indication that some of these customers may be prepared to pay a small "green premium", ultimately cost competitive pricing against rival fossil derived methacrylate is critical for commercial viability of biobased methacrylate.
The economic impact of maximising fermentable sugar transformation to saleable product delivered by the proposed technology will provide a tangible and clear commercial cost saving measure for Lucite, and consequently their customers, when the biobased manufacturing of alkyl methacrylates is deployed into production. Lucite will need to purchase less lignocellulosic feedstock to generate the same quantity of alkyl methacrylate product compared to not operating the technology seeking to be delivered within this proposal to BBSRC. Furthermore, the use of this proposed technology will add further evidence and weighting to the full sustainability credentials of biobased methacrylates that Lucite are seeking to obtain. This will increase the reputational standing of Lucite International as a responsible and ethical chemical manufacturer with its own direct customers and the wider public, which should encourage more chemical manufacturers to follow the steps of Lucite and develop greener technologies for their products. The positive outcomes of this work should also encourage more academics to seek collaboration opportunities with industrial partners, for biobased chemical and pharmaceutical manufacture.
Delivery of the proposed work will also showcase the positive contribution synthetic biology can make in addressing grand challenges such as climate change and will help to further dispel the future calls for genetically modified organism (GMO) naysayers to apply a blanket ban on GMO usage.