Natural Fruit Flavours by Biocatalysis

Lead Research Organisation: University of Oxford
Department Name: Oxford Chemistry

Abstract

The creamy, sweet, milky and desirable flavours and taste notes of apple, mango, peach, apricot, coconut, milk, cheese and butter, amongst other delicious fruits and foods are from the presence of tiny amounts of intensely flavoured natural products called lactones. Because they are found in such small quantities in fruits and other crops the material isolated from nature are very expensive. However, the demand in the flavour, food and cosmetics industry runs into tens of thousands of tonnes per annum. Almost all materials in current use are chemically synthesised from fossil fuel sources using polluting technology. Some feedstocks are harvested from the bark of trees which are killed in the process. As demand for these products increase there is a clear need for synthesis processes that are environmentally friendly and use sustainable feedstocks. The aim of this Follow-on-Fund project is to provide a one-pot process using enzyme catalysis by well-established fermentation technology.
 
Description The initial discovery phase progressed as planned, with preliminary results providing indicators for approaches to the target product and process for its synthesis.

As the enzyme evolution work progressed it became clear that both the mutations in the scientific literature and our starting mutations did not give sufficient substrate conversion to product or optical isomer purity for a viable process. However, further detailed investigations involving studies on over 100 enzyme variants enabled us to identify the mutations with detrimental effects. By the end of the project a new enzyme variant with sufficiently high activity and optical isomer ratio close to the highest grade product on the market was discovered. The high added value of this product grade has led to pre-pilot scale process development at a commercial flavours and fragrances company.
Exploitation Route The enzyme material and biocatalytic process to be developed can be scaled up to pilot scale and eventual commercial manufacturing while the academic community will gain further insight into the engineering of enzymes.
Sectors Agriculture, Food and Drink,Manufacturing, including Industrial Biotechology
 
Description The research project made sufficient progress on enzyme engineering to convert an economical feedstock from sustainable natural sources to a high-value flavour compound. The reaction system is attractive because the product will be classified as natural grade and the enantioselectivity closely matches the premium grade natural product on the market. Initial scale up trials were carried out during the project. The results are sufficiently promising for an SME to start pre-pilot scale process development towards commercial production, while a potential distributor has confirmed the current market size and the likely growth in future years. Update: During 2018 Oxford Biotrans Ltd., the spin-out company, raised further capital to scale the process further into commercial production. It achieved its first sale of the product, nootkatone, in 2018. It also won an Emerging Technology Award in the Food & Drinks sector from the Royal Society of Chemistry in 2018.
First Year Of Impact 2018
Sector Agriculture, Food and Drink,Chemicals,Manufacturing, including Industrial Biotechology
Impact Types Economic,Policy & public services
 
Description This project and its impact on the spin out company, Oxford Biotrans, was featured in an impact case study by the BBSRC entitled "Natural grapefruit flavouring from industrial biotechnology" (http://www.bbsrc.ac.uk/research/impact/natural-grapefruit-flavouring-from-industrial-biotechnology/). This is part of the review on Policy in Industrial Biotechnology by RCUK. The PI worked on this document with Valerie Nadeau (valerie.nadeau@bbsrc.ac.uk) of the BBSRC and Dr Matthew Hodges of Oxford Biotrans Ltd.
Geographic Reach National 
Policy Influence Type Citation in other policy documents
URL http://www.bbsrc.ac.uk/research/impact/natural-grapefruit-flavouring-from-industrial-biotechnology/
 
Description Business Interaction Voucher
Amount £5,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Department Networks in Industrial Biotechnology and Bioenergy (NIBB)
Sector Academic/University
Country United Kingdom
Start 01/2015 
End 04/2015
 
Description Graduate Studentship
Amount £43,000 (GBP)
Organisation Oxford Biotrans Ltd. 
Sector Private
Country United Kingdom
Start 10/2015 
End 09/2018
 
Description NIBB Metals in Biology ISCF Industrial Biotechnology Seeding Catalyst Proof of Concept grant
Amount £25,000 (GBP)
Funding ID ISCFPOCMiB035 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Department Networks in Industrial Biotechnology and Bioenergy (NIBB)
Sector Academic/University
Country United Kingdom
Start 12/2017 
End 02/2018
 
Description Industry partner 
Organisation Oxford Biotrans Ltd.
Country United Kingdom 
Sector Private 
PI Contribution The PI is a co-founder of this spin-out company and the company is interested in licensing the process for lactone synthesis that may result from the research.
Collaborator Contribution The company has provided vital links to commercial distributors and end-users for information on market size and likely future demand of the lactone target product of this research project. A project manager from the company is liaising with the PI's team on project progress and providing technical information on potential scale-up routes and process conditions on a commercial scale. There has been a small cash contribution as well (see below).
Impact Early stage programme, none directly from this research project but the company is commercialising a flavouring product from the PI's earlier work, with product launch planned for Q1/Q2, 2015. The initial commercial samples were well received. Further scale-up to commercial scale production continued and the company raised £2.5M in 2017 to enter full-scale production. Production sampling and final specifications have been completed in Q4 2017. First delivery to major customers is scheduled after June 2018. The impact of this grant has been highlighted in an Impact Case Study published on the BBSRC website (http://www.bbsrc.ac.uk/research/impact/natural-grapefruit-flavouring-from-industrial-biotechnology/).
Start Year 2013
 
Company Name Oxford Biotrans Ltd. 
Description The company has licensed two patents from the portfolio of the PI and is engaged in commercial scale-up of a biocatalytic process to produce the grapefruit flavour compound nootkatone via oxidation of valencene. The company was founded to apply the PI's P450 technology to commercialise the production of flavours and fragrances, and to the discovery and lead development in the agrochemical and pharmaceutical sectors. 
Year Established 2013 
Impact The company was founded in September 2013 and is engaged in commercial scale production trials for its first product nootkatone, the high-value grapefruit flavour compound. Initial samples were presented by De Monchy Aromatics, the marketing partner, at industry shows in 2015 and 2016. The Company established its R&D facilities at Milton Park, Didcot, Oxfordshire, employing 15 scientists in process and new product development. The premises was officially opened by Nicola Blackwood, MP, in March 2016. Oxford Biotrans has since developed the process further, achieving commercial scale (cubic metres) reactions in Q4 2016. Full production and commercial launch is planned in Q3 2017, at which point the profits from sales will enable the company to be self-financing. Further VC funding is being considered for expansion of the product portfolio into other sectors. The Company has been featured in, e.g. the Daily Telegraph and the RSC publication Chemistry World.
Website http://www.oxfordbiotrans.com
 
Description Outreach Activity: Residential Taster Course at Oxford University for students considering applying to STEM subjects and Chemistry in particular 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact As part of the Outreach Programme of the Department a cohort of up to 30 students from all over the UK who are about to apply to universities are selected on the basis of UCAS contextual data in order to broaden participation in higher education, in particular in STEM subjects, by those from underprivileged backgrounds. Since 2014 I deliver a lecture on biological synthesis pathways to flavour and fragrances and biologically active compounds from plants and microorganisms and, most importantly, use these to illustrate fundamental concepts in chemistry, biochemistry, biology and engineering. The aim is to broaden the horizons of the students and to inspire them to view a degree in STEM subjects as the providing the basic skills and training for a wide range of careers in science, R&D, engineering and teaching. After the lectures the students are given an afternoon session in the practical laboratories to see how state-of-the-art instrumentation and techniques are applied to solve problems. Feedback has been universally positive, highlighting the diverse audience participation, the informative nature of the lectures and especially the broad view of science and technology that students had rarely been exposed to before. The application rate to STEM subjects in 100%, and up to 20% per year have been accepted to the Oxford Chemistry degree course.
Year(s) Of Engagement Activity 2014,2015,2016
URL http://outreach.chem.ox.ac.uk/