Blending Together Synthetic Chemistry and Synthetic Biology For Catalysis

The focus of this project is on the identification of novel halogenases. Public databases will be mined using protein BLAST and a set of conserved motifs known to be present in halogenases. A motif has been identified within the Goss group which allows accurate identification of a halogenase from a set of otherwise similar proteins. The resulting list of hits is then narrowed down using a variety of software and online resources. By in silico assessment of the likely three-dimensional structure and of the evolutionary origin of the candidate halogenases enables the determination of unique halogenases for study and progression.
Once the halogenases have been selected in silico synthetic genes are purchased and cloned into pUC19 as a storage vector and into pSG181, an expression vector developed in the group which contains a TEV cleavable octa-histidine tag at the N-terminus. Optimal conditions for protein production and purification will be assessed. Once they are determined, large scale production of each of the proteins will be carried out. The purified enzymes will then be tested against a substrate library to identify the types of compounds they are able to halogenate.
Any interesting compounds that are successfully halogenated will be further derivatised by palladium catalysed cross coupling under mild conditions to generate analogues. Other work may involve the engineering of halogenases to improve stability, activity or substrate scope. Other branches of the work will focus on the engineering of microbial biosynthetic pathways to generate unnatural natural products which will contain the Carbon-halogen bond acting as a functional handle to allow further derivatisation of the products by cross coupling.

Catalysis is an inherently transformative field and the single most powerful method to reduce cost, energy demand and ensure sustainable fine and commodity chemical manufacture. On a grander scale, we will advance the UK economy, security and health through the development and understanding of catalysis. Through an intensive training programme we will ensure optimal use and recovery of our critical resources, exploit new long-term sustainable resources and feedstocks and will make chemical manufacture fit for future generations. Above all we will develop technologies offering a step-change in resource management and utilization. Specific impacts include:
Industry: The UK is an emerging leader in chemical sustainability. Critical Resource Catalysis is thus inherent to the growth of a technology-driven UK economy. In 2007, the growing chemical industry supported 6 million jobs and 21% of the UK GDP. World-class academic researchers, a broadly educated PhD cohort, inherent industrial collaboration and a holistic training environment will deliver unique individuals and scientific outputs for the chemical industry and beyond. Over 95% of our PhD students have continued their scientific efforts, sharing expertise in postdoctoral and industry positions: we produce exceptionally valued workers. The enhanced training provision provided by this CDT ensures even greater demand. Our training is intrinsically linked to industry and private sector parties, delivering core scientific knowledge and translational skills. With expertise in delivering critical innovations to industry, CRITICAT will become the hub for business and industry collaboration, consultation and discovery in the UK and beyond.
Policymakers: Global governments are recognising how important resources are to quality of life. The UK is committed to policies that demand the development of new technologies to facilitate a sustainable lifestyle, including the decarbonisation of energy supplies and the recycling of products, in particular those which contain a critical resource. With a cohort versed in the scientific and sociological arguments surrounding these issues further equipped to tackle future scientific challenges we will supports and strengthens the policies set out by the UK government and will serve as a champion for clear policy direction in the future.
Public: Educating not only our cohort but the general public about the importance of Critical Resource Catalysis is essential. We will engage with beneficiaries, from general audiences to UK HEIs, on our finite resources, their economic impacts and the societal benefits of a sustainable chemical industry. Public science demonstrations, focusing on the chemistry and engineering of critical resources, their uses in today's leading technologies, and the exploitation of the catalytic chemical sciences in a sustainable lifestyle will be led by the cohort to provide the public with a balanced and reasoned view of our contributions. With extensive expertise in public engagement, our team of educators and leaders will drive engagement activities forward and train our cohorts to develop as broad-skilled champions of chemistry and catalysis.
Dynamic researchers: This CDT will deliver at least 80 newly qualified PhD scientists and engineers who are trained in catalysis, the key driver behind sustainable chemical technologies. The students will undertake an exceptionally broad training regime enhanced well beyond a traditional PhD programme. Combined with state-of-the-art research projects, the collaborative interactions intrinsic throughout the CDT will yield great foundational and transferable skills for both researchers and institutions. They will learn business, managerial and communication skills from bespoke training, collaborative science and industry placements. Long-term impact will be ensured through our cohorts' entry into the global workforce and our universities commitment to improved collaboration and pedagogy.