Cellulect: A Synthetic Biology Platform for the Optimization of Enzymatic Biomass Processing

It is widely recognised that humankind must move to sustainable ways of manufacturing and that this will necessitate our adoption of chemical feedstocks derived from plant-based material known as biomass. The goal is to allow biomass which is currently a waste product of farming, like straw, to be converted into sugars and then used to manufacture useful products. We propose to develop a "front-end" to optimise the conversion of biomass to sugars. This technology may be bolted to any "back-end" in a biorefinery to produce anything from biofuels to bioplastics and so on. By creating a technology for the rapid tuning of a bacteria or fungus for the best biomass conversion, we stand to diversify the range of raw biomass feedstocks which may be exploited efficiently.

The work proposed herein creates a novel technology for biomass feedstock to be screened against a library of enzymes to determine which gene combinations give the optimal biomass degradation. These combinations may then be used as a starting point to generate further combinations in an evolutionary process. This will create value for the user in terms of improvements in the yield of biomass conversion to useable feedstock.
In addition to enabling the optimisation of enzyme blends for any given application, analysis of the results will allow the team to develop heuristics which will facilitate rational design of biomass processing systems in the future, and will lead to a deeper understanding of biomass degradation processes.

The technology developed will be offered to the marketplace by our commercial team members, Ingenza Ltd. There are a number of routes to value extraction including: i.) Biomanufacture of bulk quantities of the enzyme blend for sale direct to biorefinery operators as cell lysate or extract. ii.) Alternatively, the clone itself could be sold to a customer, to generate their own enzymes. We anticipate that this would involve a licensing agreement. iii.) Provision of a contract service to customers wishing to have a bespoke digestion chassis implemented for the particular biomass of interest to them; probably involving some form of strain maintenance and further modification as required.

We propose to develop and implement a genetic platform for optimizing blends of enzymes for biomass processing applications, using computational modeling, combinatorial gene assembly, expression control and high-throughput screening of gene cassettes from a library of genes in modular format. In addition to providing optimal enzyme blends for any given application, analysis of the results will allow us to develop heuristics which will facilitate rational design of biomass processing systems in the future, and will lead to a deeper understanding of biomass degradation processes.

The expected results are:
1 To generate a library of modular genetic parts encoding biomolecules active in biomass degradation;
2 To create a portfolio of bacterial / fungal strains with optimised degradation performance for key industrially-relevant types of biomass;
3 To define the design rules for what biomolecules are required for effective biodegradation.

Exploitation will be achieved by industry partner Ingenza who provide a ready route to exploitation of this high-throughput platform technology via sale of enzyme cocktails (direct or by third party), licensed production of proprietary engineered strain to third party and/or contracted development of custom biomass-optimised strain.

It is abundantly apparent from the recent influx of industry leaders in many commercial sectors, eager to consider and investigate industrial biotechnology and synthetic biology routes to their products that many in manufacturing industry have begun to understand the need for sustainability through biotechnology. It is essential that biotechnology developers and providers in academia and industry recognise the need to continually improve the predictability with which biotechnology can demonstrate feasibility and deliver results rapidly. The Cellulect team believes that success of the enabling technology being developed in this project will contribute greatly to a necessary step change in the ability to implement competitive economic processes using cellulosic biomass.

The project can demonstrate an extremely strong and direct commercial fit through our partner company, Ingenza Ltd. The technology developed is highly synergistic with Ingenza's existing strain development programmes in biofuel, sustainable manufacture of chemicals and many other areas. In addition to the applications already described with market leaders in bioethanol and polymer production, Ingenza is engaged at the feasibility and proposal stages with 4 additional large scale industrial partnerships, in which the efficient use of cellulosic biomass is a critical element of long-term success. Therefore, Ingenza provides a gateway to many end-users thus ensuring an immediate and substantial impact on industrial practise.