CBET-EPSRC - Grown Engineered Materials (GEMs): synthetic consortia for biomanufacturing tunable composites

The 20th century saw unprecedented advances in the manufacture of materials, with chemical and mechanical engineering approaches enabling plastics, composites, aerogels and more. Now in the 21st century, our newfound abilities in biological engineering open the door to a new paradigm - Grown Engineered Materials (GEMs). Rather than blending together and chemically-modifying existing bulk materials ex situ, GEMs will be produced in vivo in the precise, sustainable way that materials are made by nature - with cells working together at the micro scale to grow different polymers in parallel that interact to form self-patterned composites.

Using a synthetic biology approach, this breakthrough project will develop and demonstrate the first generation of GEMs, producing these by co-cultivating a set of engineered microbes that we have demonstrated can be grown together as a stable consortium. These material-producing microbes will produce GEMs made from nanocellulose fibres and elastin-like polypeptides (ELPs). These are both repetitive biopolymers that on their own have industrially-attractive properties; bacterial-made nanocellulose is exceptionally pure, biocompatible and possess a high mechanical load capability, while yeast-made ELPs are environment-responsive and can be designed to collapse or extend due to changes in levels of salt, pH or temperature. Having these two biomaterials co-synthesised together from growing engineered cells offers a novel route to making exciting new materials that offer properties beyond those of their constituent parts. This approach is inspired by nature, where we witness plants building impressive biomaterials from weaving cellulose into a mechanically-robust composites by incorporation of different polymers such as lignin. For example, the natural co-production of cellulose in composites with other biopolymers enhances the compressive strength of plant cell walls and also enables new characteristics to emerge.

To demonstrate the paradigm of GEMs, our UK and US groups will work together in this project to synthesise and test different ELP designs for how the proteins interact within a growing nanocellulose fibre network. Alongside this we will study, engineer and optimise yeast strains so that these ELP proteins can be efficiently secreted into the growing material by engineered yeast cells that stably co-culture with the cellulose-producing bacteria. By the end of the project we expect to be able to grow high yields of ELP-cellulose composites in just a few days from only our mix of yeasts and bacteria and low-cost growth media. We will assess the material properties of these prototype GEMs and then use synthetic biology tools, such as optogenetics and pattern formation to control how, where and when the composites are made at the micro-scale.

This ambitious interdisciplinary research project will utilise many state-of-the-art approaches to biological engineering that our two groups have international expertise in. From synthetic protein polymer design, strain optimisation and synthetic biology genetic control, right through to systems biology, transcriptomics, machine learning and biomaterial characterisation. We plan to produce a range of ELP-cellulose composite materials that are genetically-tunable, so that changes in the way DNA is written in the microbial cells can predictably lead to changes in the materials and their properties. Our aim is to realise the paradigm of GEMs and provide the blueprint, engineered strains and synthetic biology toolkit for others to utilise this approach in the future.

The proposed work spans foundational research and engineering right through to applications that yield new materials and a new biomanufacturing paradigm. As such it is an exemplar interdisciplinary project - one designed to produce new advanced, sustainably-made products that cannot yet be realised by any other means. We expect the GEMs approach to have long-term impact on UK and US engineering sectors, and industrial manufacturing throughout the value chain. Importantly for the UK, the project links together Synthetic Biology and Advanced Materials - two of the Eight Great Technologies highlighted to advance UK productivity in this decade and beyond. Bridging these areas of expertise will likely catalyse significant downstream wealth creation by aiding in developing new companies and new technologies with a wide array of future applications. The use of engineered biology for novel materials biomanufacture is one that will likely attract significant investment, along with widespread research and media interest.

The applied part of this project will open up new avenues of applications of engineered biology, which is currently focused on fine chemical and biochemical production or health-related uses. GEMs offer a route to use synthetic biology tools being developed in the UK and US towards making new products that could improve existing industries (e.g. filtration, textiles, advanced composites) or may even yield an entirely new industry sector of its own (e.g. sensing and responsive materials).

The development of materials from ELP-cellulose will also aid applications in industry and we expect IP to be generated in this area. We anticipate early impact in products and sectors where microbially-produced cellulose is already in use, as these industries can adopters more advanced versions of nanocellulose fibres grown as functional or smart composites with other biopolymers or proteins. Microbially-produced cellulose is currently used in applications in food technology, wound dressing, surgery, filtration, batteries and audio equipment, and so it is likely that GEMs will impact a diverse set of sectors. Already we have begun discussions on applying cellulose-based GEMs as protective materials for the UK and US defence sectors (via DSTL and US Army) and in filters for wastewater decontamination (via Customem Ltd). There is also great interest from the areas of textiles and design, and collaborations here can give us an opportunity to explore alternative areas of impact.

The project will also impact greatly on commercial production of proteins and biopolymers for biotechnology products. Our research will yield new design rules and yeast strains capable of over-production and secretion of synthetic proteins, which could be used in other applications and sectors. Many of the most exciting and profitable uses of engineered biology that are now emerging, such as in spider silk production for materials (by Bolt Threads, AMSilk) and globin production for meat-free foods (e.g. Impossible Burger) need overproduction of proteins from yeasts for their key ingredients. Strains engineered for boosted protein secretion will generate valuable IP, offering licensing opportunities to the many companies who are currently limited by protein production yields.

Our foundational work also offers impact in the rapidly-growing industrial synthetic biology sector by demonstrating how multiple engineered strains can be used in consortia to fulfill a specific task. Efficient and stable division of labour between different engineered cells is a key challenge for expanding complex biosynthesis into industrial biotechnology processes. The attached Pathways to Impact document further details how we anticipate working with companies and promoting our work to the general public, and how we will exploit knowledge generated in the project and promote future research collaborations both inside and outside our fields.