Bioactive terpenoids as high performance ingredients for industry

For the UK to achieve its Net Zero targets there is an urgent need across industrial sectors to replace the reliance on petrochemical based feedstocks with sustainable bio-based feedstock. Croda is a UK based multinational company and global leader in high performance ingredients and technologies that are found in some of the most successful brands in the world across a wide range of markets including Personal, Health and Crop Care. Croda has recently undertaken an Executive Committee level product portfolio review and identified a need to focus innovation activities upon industrial biotechnology as a route to sustainable and biobased ingredients across a broad range of areas.
Terpenoids represent one of the largest and most diverse classes of natural products in the world, providing an array of functionalities for different industry sectors ranging from flavour and fragrance to human health and personal care. The Graham laboratory at the University of York is world leading in the discovery and development of different classes of terpenoids from plants and have recently been collaborating with Croda to explore the potential of using these to replace petrochemical derived products in the company's portfolio of ingredients being supplied across a range of industrial sectors. Based on proof of concept work, it is clear there is huge potential. The challenge is that many of these terpene based natural products are not available at commercial scale as they are currently only available in relatively small amounts from the plants that produce them. This project will address this challenge by establishing the biosynthetic route to selected terpenoids that perform in Croda's proprietary platforms and by using a combination of synthetic/engineering biology and industrial biotechnology develop new production platforms that will allow commercial scale-up and development of new biobased products. Croda already have expertise in fermentation based scale-up in so called heterologous host platforms that will complement the gene discovery and laboratory scale engineering of host platforms that will be performed at the University of York. Early leads have already been identified for the Crop Care sector which could have a major impact on the sustainability of agriculture.

Plants produce a remarkable array of chemicals, among which the terpenoid class are particularly interesting to industry with specific types being used across the pharmaceutical, agricultural, personal, home-care and fragrance sectors. These are often sourced from a limited number of low-yielding species, restricting their supply and greatly increasing their cost. Gene discovery, metabolite analysis and engineering biology has allowed the Graham laboratory at the UoY to produce a variety of di- and triterpenoid molecules and secure IP on novel biosynthetic genes. Proof of concept work already conducted by Croda Canada in partnership with UoY has involved screening a range of terpenoids using the company's proprietary in-vitro platforms resulting in the discovery of novel adjuvant activities that are superior to commercially deployed fossil feedstock derived adjuvants when used in crop care formulation with several different fungicides.This proposal builds on these discoveries and will prioritise development of tools and platforms for scaling up production of lead compounds for glasshouse and field trials. Selection and development of alternative heterologous production systems for industrial biotechnology scale-up will be prioritised by the industrial partner. The partnership will apply the same approaches across the companies personal and health care sectors and will target the sustainable production using industrial biotechnology of other terpenoids with proven functionality. Adding sugar moieties to bioactive natural products can improve solubility, bioavailability, stability and efficacy. A dedicated work package will use a proven glycosylation platform to identify specific enzymes that glycosylate selected bioactive terpenoids and the outputs of this will be further evaluated across the Croda screening platforms prior to scaling up production in microbial host systems.