The scent of the rose is one of the most sought after in the fragrance industry and for more general domestic as well as personal products. Eau de toilette contains the lighter, more volatile rose essential oil components such as citronellol and geraniol. Perfumes are longer lasting as they contain less volatile components such as the rose ketones damascone, damascenone, ionones and the like. Another component of rose essential oil is the small molecule rose oxide. Although present in tiny amounts in rose oil, it has an odour threshold of 0.5 parts-per-billion and contributes more to the rose note than all other compounds except for damascone. Rose oxide is described as having a floral, green note and so important that a stamp with its molecular structure printed on it was issued when the compound was first isolated from the oil of Bulgarian roses. Rose oxide is a high value fine chemical because it takes 3 tonnes of rose blossoms to generate 1 kg of rose oil which contains <0.1% rose oxide. Material isolated from natural sources is expensive ($7,000 per kg). Commercially, rose oxide is produced by chemical routes from citronellol; one route uses bromine while others require reagents that are polluting to produce and use. The aim of this project is to develop a biological process to rose oxide from citronellol, with the key step being the oxidation of a specific carbon-hydrogen bond in citronellol. These bonds are chemically inert, which leads to more complex routes or more polluting processes in order to use citronellol as feedstock. We have developed enzyme variants capable of carrying out this critical step in water at ambient temperature. The industry partner for the project is in the process of taking this to commercial scale rose oxide production by a sustainable and non-polluting biotechnological process. The purpose of this project is to develop more active enzymes and alternative feedstocks based on citronellol in order to make the rose oxide process even more efficient and productive. Advanced computational methods will also be applied to help guide enzyme design and process development.

Synthetic Biology is the underpinning discipline for advances in the UK bioeconomy, a sector currently worth ~£200Bn GVA globally. It is a technology base that is revolutionising methods of working in the biotechnology sector and has been the subject of important Government Roadmaps and supported by significant UKRI investments through the Synthetic Biology for Growth programme. This is now leading to a vibrant translational landscape with many start-ups taking advantage of the rapidly evolving technology landscape and traditional industries seeking to embed new working practices. We have sought evidence from key industry leaders within the emerging technology space and received a clear and consistent response that there is a significant deficit of suitably trained PhDs that can bridge the gap between biological understanding and data science. Our vision is a CDT with an integrative training programme that covers experimentation, coding, data science and entrepreneurship applied to the design, realisation and optimisation of novel biological systems for diverse applications: BioDesign Engineers. It directly addresses the priority area 'Engineering for the Bioeconomy' and has the potential to underpin growth across many sectors of the bioeconomy including pharmaceutical, healthcare, chemical, energy, and food. This CDT will bring together three world-leading academic institutions, Imperial College London (Imperial), University of Manchester (UoM) and University College London (UCL) with a wide portfolio of industrial partners to create an integrated approach to training the next generation of visionary BioDesign Engineers. Our CDT will focus on providing an optimal training environment together with a rigorous interdisciplinary program of cohort-based training and research, so that students are equipped to address complex questions at the cutting edge of the field. It will provide the highly-skilled workforce required by this emerging industry and establish a network of future UK Bioindustry leaders. The joint location of the CDT in London and Manchester will provide a strong dynamic link between the SE England biotech cluster and the Northern Powerhouse. Our vision, which brings together a BioDesign perspective with Engineering expertise, can only be delivered by an outstanding and proven grouping of internationally renowned researchers. We have a supervisor pool of 66 world class researchers that span the associated disciplines and have a demonstrated commitment to interdisciplinary research and training. Furthermore, students will work directly with the London and Manchester DNA Foundries, embedding the next generation bioscience technologies and automation in their training and working practices. Cohort training will be delivered through a common first year MRes at Imperial College London, with students following a 3-month taught programme and a 9-month research project at one of the 3 participating institutions. Cohort and industry stakeholder engagement will be ensured through bespoke training and CDT activities that will take place every 6 months during the entire 4-year span of the programme and include multi-year group hackathons, training in responsible research and innovation, PhD research symposia, industry research days, and entrepreneurial skills training. Through this ambitious cohort-based training, we will deliver PhD-level BioDesign Engineers that can bridge the gap between rigorous engineering, efficient model-based design, in-depth cellular and biomolecular knowledge, high throughput automation and data science for the realisation and exploitation of engineered biological systems. This unique cohort-based training platform will create the next generation of visionaries and leaders needed to accelerate growth of the UK bioeconomy.

The pharmaceutical, chemical and polymer industries are cornerstones of Europe's economy. A key element for their transition to more sustainable processes and to innovative new compounds is biocatalysis. Of particular interest are metallo-enzymes, i.e. proteins that host a metal cofactor. They catalyze a multitude of redox and radical reactions. To access reactions that are unknown in nature, artificial metallo-enzymes can be created. They combine the new-to-nature catalytic activity of metal complexes with the selectivity-inducing environment of the active protein site. To develop novel biocatalysts, a highly interdisciplinary skill set is needed. MetRaZymes will create a PhD school across leading European universities that will train the next generation of scientists capable of tackling the design, development and implementation of novel enzymatic reactions in a holistic approach. It brings together computational bioscientists, bioinorganic and polymer chemists, and bioprocess engineers. Using artificial and repurposed metalloenzymes as the focal point, the ESRs will develop novel biocatalysts for radical reactions of high synthetic value, such as the late stage modification of pharmaceutical intermediates or the synthesis of polymers from renewable monomers. To train the ESRs in the needs of industrial biotechnology, the consortium includes eight of Europe's leading pharmaceutical, chemical and enzymology companies. The ESRs will benefit from a vast transferable skills training program delivered by five training partners. Highlights include a Nature Masterclass and Wikipedia workshop. Communication partners such as Wikimedia and the Industrial Biotechnology Innovation Centre will act as muliplicators for the communication of results. Moreover, the ESRs will work with artist that use biology as their way of expression to create an ARTzymes exhibition that will foster the ERS's creativity and result in a an unique form of science dialogue with the general public