Details of Grant 

EPSRC Reference:	EP/Y003314/1
Title:	Investigating biosynthesis of the newly discovered natural product euglenatide and distribution across the breadth of Euglenoid algae
Principal Investigator:	O'Neill, Dr E
Other Investigators:
Researcher Co-Investigators:
Project Partners:	Trent University Canada
Department:	Sch of Chemistry
Organisation:	University of Nottingham
Scheme:	Standard Research - NR1
Starts:	01 April 2024	Ends:	31 March 2025	Value (£):	157,085
EPSRC Research Topic Classifications:	Biological & Medicinal Chem.
EPSRC Industrial Sector Classifications:	No relevance to Underpinning Sectors
Related Grants:
Panel History:	Panel Date Panel Name Outcome 24 May 2023 ECR International Collaboration Grants Panel 3 Announced
Summary on Grant Application Form
One third of all pharmaceuticals are based on natural products, most of which are currently derived from bacteria, fungi and plants. Algae are a largely untapped source of these drug-like molecules and this research program will focus on these to understand the production of highly valuable compounds. We have found that the alga Euglena produces a natural product with antifungal and anticancer activity, which we called euglenatides. We want to find out how these molecules are made, how widespread they are and what other potential new drugs are made by these algae. This project is a collaboration between a group at Trent University in Canada who are experts in isolating and genome engineering Euglenoid algae, and a group at the University of Nottingham with expertise in Euglena natural product identification. Microbes interact, whether in competition or collaboration, through released chemicals and many of the natural products involved have been co-opted by us as pharmaceuticals. These include some of the most critical antibiotics, including penicillin and erythromycin, and cancer medicines, such as doxorubicin. Algae are a diverse group of organisms that, despite tantalising evidence for a vast capacity for natural product synthesis, have remained largely unstudied. A few species of algae produce highly toxic compounds, only discovered when harmful algal blooms, such as red tides, cause poisonings in humans and animals. If we tune this toxicity to only act against bacteria or cancer cells, we can turn toxins into medicines. There is evidence that many other types of algae make a wide range of bioactive compounds, which have the potential for us to use as antibiotics or anti-cancer agents. The algae we are going to work on in this research program are Euglena, a group of single-celled algae, which are distantly related to green algae. They are found in freshwater ponds and ditches, all over the world, and some species are used in a wide range of research and applications. Euglena produce an extraordinarily broad range of compounds, including antioxidants, vitamins and brain-nourishing polyunsaturated fatty acids, even grown in wastewater. This has led to the development of Euglena as a food supplement and ongoing work to produce carbon neutral biofuels at a commercial scale. There is great promise from their ability to grow on land unsuitable for agriculture, with minimal inputs, achieving significantly higher yields than from conventional crops, and there is a growing interest in engineering them to produce high value proteins and pharmaceuticals. We have found that the Euglena genome encodes genes for producing a wide range of natural products that will be highly valuable if we can realise this potential. The wide range of academic and industrial research into Euglena will help to rapidly translate the results of this project into societal benefits. The research plan we are proposing will initially use genetic engineering in a well-studied lab strain to delete specific genes we propose may be involved in the synthesis of the euglenatides. We will then see which changes prevent any production and which make other products. We will then look at new strains of Euglenoid algae from the freshwater lakes in Ontario to see if wild strain of these algae can make euglenatides. We will also investigate production of other molecules in these new cultures of Euglena. Our preliminary research suggests this type of algae has a large biosynthetic capacity to make interesting molecules and this research program will allow us to explore them extensively. By working in these under studied organisms we maximise our opportunities to find compounds that have never been seen before, which will then be advanced as bioactive probes and drug candidates. The unique pairing of genome editing tools in a euglenatide producer gives us an unprecedent chance to study the natural product biosynthetic pathway. .
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Organisation Website:	http://www.nottingham.ac.uk