Novel formulation design strategy

Bio-inspired processes will have a major impact on the global society in 21st Century. The employment of biocatalysts in industrial processes is expected to boost a sustainable production of chemicals, biopolymers, materials and fuels from renewable resources. In this context, the ability of proteins from psychrophilic and thermophilic organisms to be functional under extreme temperatures is attracting considerable interest both from academia and industry. Cold adapted enzymes, for example, are appealing targets to optimise energy efficient industrial processes at low temperatures.

The scope of this proposal is to translate academic research into industrial applications by exploiting techniques and methods developed in nuclear magnetic resonance of proteins to allow the exploitation of biocatalysts (including psychrophilic enzymes) in biotechnological processes.

In this context, the proposal aims at a radical innovation in the characterisation of the biological processes by which enzymes exert their catalytic function, under natural or biotechnological conditions. To this end, we propose a powerful multiscale approach that integrates experiments and theory toward an accurate characterisation of complex molecular dynamics and interactions. The methods will have a pivotal role in elucidating new mechanisms of strategic relevance for nano- and bio- technologies.

As a development case, we will focus on the development of a new enabling technology for the characterisation of biomolecular processes occuring at liquid-liquid and liquid-solid interfaces into the domain of industrial biotechnology. The project will therefore allow us explore and mature the technology further towards integration into the production process for commercial products at the required scale, specificity and cost, in the first instance for home and personal care (HPC).

In the present project we will use new interdisciplinary approaches of biomolecular NMR and molecular simulations to characterise the relevant dynamics that govern the activity of lipases during their activity under native conditions and in biotechnological applications.

Multiscale approaches will be implemented using full-atom simulations instructed by solution (RDC, relaxation, H/D exchange) and solid state (chemical shifts, distances, CSA and DC) NMR experimental data. These methods will describe multiple levels of protein dynamics and achieve an understanding of the key pathways of structural conversions of the protein in its biological activity.

Overall, we will employ a battery of NMR measurements combined with cutting-edge methods for structural refinement to understand the molecular mechanisms governing lipase function, under the different conditions planned in this project. Using this approach, we will be able to delineate the structure/dynamics/function relationship in this enzyme and identify relevant factors to improve the way by which the enzyme is used in biotachnological applications.
Expected outcomes include:
-Characterising the relevant timescales for functional dynamics in lipases working at low/high temperatures.
-Understanding the effects of environmental factors on the relevant functional dynamics of the enzymes.
-Define a new approach based on new tools and knowledge that will transform the design of formulations employing biocatalysts

As described in proposal submitted to Innovate UK