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Directed Protein Evolution for Synthetic Biology and Biocatalysis

Periodic Reporting for period 1 - ES-Cat (Directed Protein Evolution for Synthetic Biology and Biocatalysis)

Reporting period: 2017-03-01 to 2019-02-28

The ES-Cat (Evolution, Synthetic Biology, and Biocatalysis) Research Consortium aims to use directed evolution to reproduce and improve upon the remarkable biological catalysts (enzymes) found in nature. Enzymes are largely selective, efficient, and ‘green’; chemical reactions that may otherwise require high temperatures or pressures, harsh solvents, or toxic metal ions can be catalysed by enzymes in comparatively mild conditions. The exploitation of enzymes is limited, however, by the immense complexity of these biological molecules. The process of Darwinian evolution has shaped naturally occurring enzymes to fill their requirements in nature, so if we wish to harness the catalytic power of enzymes for non-natural reactions or reactions on substrates of our choosing, we must engineer them to suit our needs.
The ES-Cat Consortium, therefore, is designed to share and combine complementary approaches to enzyme engineering, and to empower Early Stage Researchers (ESRs) with the tools required to generate efficient biocatalysts for application in biomedicine, biotechnology, and cell biology.
The objectives of the Action are broadly:
• to involve ESRs in design and application of innovative strategies for industrial protein engineering that integrate directed evolution, powerful computational methods, and miniaturized high-throughput experimentation
• to engage ESRs in collaborative projects with industrial partners interested in robust proteins for use in applied biocatalysis, or medicine.
• to train ESRs as creative researchers able to develop and apply novel methodologies in tailoring enzymes and other proteins for industrial application, by guidance and frequent contacts with PIs from the network, and through participation in scientific events.
• to train ESRS in awareness of societal context of molecular biotechnology and of the industrial opportunities and challenges, as well as to equip them with the ambition and skills required for a successful career in industries contributing to the Europe’s competitive bioeconomy
• to disseminate the vision, activities and results of the ES-Cat network to the outside world by workshops and symposia open to other EU project participants and network members, and their home institutes. In addition to making the case for the use of directed evolution in protein engineering, we will endeavour to raise citizen awareness by engaging with the public via open days, MC ambassadorships and social media.
In this first reporting period, most deliverables have been related to establishing management processes, recruiting ESRs, assessing training needs, and completing ethics requirements. The successful implementation of these deliverables was necessary for the commencement of the scientific research to be undertaken throughout the remainder of the Action. To summarise, we have appointed teams for network management, established a supervisory board, finalised a Consortium Agreement between beneficiaries, and recruited 15 outstanding ESRs from a pool of over 300 applicants. An ES-Cat Kick Off Meeting provided opportunities for ESRs and their supervisors to meet with the rest of the Consortium and commence scientific discussion and planning. Workshops on a variety of topics and techniques have been run: an introduction to state-of-the-art molecular evolution, bioinformatics and phylogenetic reconstruction, implementation of screening and selection processes necessary for this evolution (including droplet compartmentalization, and phage and ribosome display), a Summer School on biocatalysis, a more general workshop on the process of drug development, and workshops focusing on vital facets of research including ethics, communication, and entrepreneurship. These workshops have equipped ES-Cat ESRs with the necessary skills to not only perform cutting-edge research, but also to use best-practices for dissemination and valorisation of their results. Research in the ES-Cat network has commenced; computationally stabilized libraries of aminotransferases have been designed and the validity of protein stabilising protocols has been validated; work has been done to characterise re-designed enzymes for food technology applications; and methods of developing focused libraries have been validated using a deacetylase model enzyme.
The work being carried out in the ES-Cat network makes use of cutting-edge technologies to explore novel facets of biocatalysis. Specifically, the research being done in the first half of this broad project is stocking a toolbox that can be applied to not only enzymes being studied in the scope of ES-Cat, but to all biocatalytic processes. Generating robust libraries, assays, and engineering efforts will benefit the generation and application of biocatalysts in medicine, industry, and bioremediation.
ESRs and PIs at kick off meeting
ES-Cat Logo
ESRs at UCAM workshop