Chemical synthesis using precursors from petrochemical refining is the production method of choice for a wide range of multi-sectorial products including household goods and pharmaceuticals. The dwindling fossil fuel reserves and unfavourable environmental credentials (including climate change) means the develop of renewable sources to create a bioeconomy is necessary.
Yam (Dioscorea species) are known to be a rich source of secondary/specialised metabolites with proven industrial value. Historically, species of Dioscorea have been an important source of diosgenin, used for the partial synthesis of steroidal drugs. It is clear from recent phylogenetic studies of Dioscorea that the opportunity exists for new sources of these compounds and there precursors. Our recent metabolomics studies have revealed a plethora of valuable chemical constituents among yam species. These chemical entities include shikimic acid. This molecule is the precursor for the semi-synthesis of the anti-influenza drug oseltamivir (Tamiflu). The market for this drug is $1.8 billion per year. During pandemics world shortages arise. Other examples of high value chemical/pharmaceuticals that could be sourced from yam include L-Dopa (and other catecholamines) a psychoactive agent used in the treatment of Parkinson’s disease and dopamine in response to dystonia. The successful candidate will use state of the art metabolite profiling approaches (LC-MS and GC-MS) that have been established in the lab to assess diverse yam accessions (available at Kew Botanical gardens) for high value biological active compounds. These biogenic feedstocks will be evaluated as new feedstocks for potential biorefining cascades. The data generated will provide short-term impactful biosources for bioactives. In a complementary approach the programme will focus on the terpenoid class of compounds found in yam and demonstrate the potential of: (i) engineering heterologous yam derived biosynthetic pathways into the non-conventional yeast Xanthophyllomyces dendrorhous (Phaffia rhodozyma). This organism is a high terpenoid producer and optimised for the production of terpenoids and (ii) the use of biocatalysts and other industrial microbes to perform biotranformations to potentially deliver new structural analogies with new and repurposed biological activities. Such an experimental programme will provide the candidate with first-hand experience in modern biochemical (including analytical chemistry) and Molecular Biology. All carried out in an applied environment that is synergistic with the UKs Industrial policy for clean growth and industry biotechnology. Related references are provided below.
This PhD project will be supervised jointly by:
1. Prof Paul D. Fraser, Department of Biological Sciences, Royal Holloway University of London
2. Dr Paul Wilkin, Head of Natural Capital and Plant Health
Applicants are invited to contact supervisor(s) by email ahead of submitting their application. Further information about applying for a postgraduate course at Royal Holloway can be found here: https://www.royalholloway.ac.uk/studying-here/applying/postgraduate/how-to-apply/
Applications should be submitted online: https://admissions.royalholloway.ac.uk/#/HEapplicationForm////////1
Nogueira, M., Enfissi, E.M.A. Welsch, R., Beyer, P. Zurbriggen, MD., and Fraser, PD.. (2018). The construction of a fusion enzyme for astaxanthin formation and its characterisation in microbial and plant hosts: A new tool for engineering ketocarotenoids. Metabolic Engineering, 52, 243-252.
Nogueira, N, Enfissi, EMA, Maria Martinez, M., Menard GNC, Driller, L, Eastmond, PJ., Schuch, W, Sandmann, G and Fraser, PD. (2017) A new plant-based source of ketocarotenoids for aquaculture feed. PNAS, 114, 10876-10881.
Price, EJ., Bhattacharjee, R., Lopez-Montes, A. & Fraser, P.D. (2017) Metabolite profiling of yam (Dioscorea spp.) accessions for use in crop improvement programmes. Metabolomics. 13:144.
Price, E., Wilkin, P., Sarasan, V. & Fraser, P.D. (2016). Metabolite profiling of Dioscorea (yam) species reveals underutilised biodiversity and renewable sources for high-value compounds. Scientific reports. 6, Art No 29136.
Price EJ., Drapal M., Perez-Fons L, Amah, D., Bhattacharjee, R.,, Heider B., Mathieu Rouard, M., Swennen,R., Becerra Lopez-Lavalle LA., and Fraser, PD. Metabolite database for root, tuber and banana crops to facilitate modern breeding in understudied crops, The Plant Journal, in press.