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Award details

Developing platforms for the production of diterpenoids (TSB application reference 43970-304155)

ReferenceBB/M018210/1
Principal Investigator / Supervisor Professor Ian Graham
Co-Investigators /
Co-Supervisors		 Dr Andrew King, Professor Margaret Smith
Institution University of York
DepartmentBiology
Funding typeResearch
Value (£) 2,397,566
StatusCompleted
TypeResearch Grant
Start date 01/04/2015
End date 30/09/2021
Duration78 months

Abstract

The project will address issues of supply and high production costs of selected high value chemicals of particular interest to its industrial partners (GSK, Unilever and Croda) and will provide advances in technology for wider applications across UK research and industry. Currently a number of plant diterpenoids are used in the pharmaceutical, agricultural, food additive and fragrance industries. These are sourced from a limited number of species, restricting their supply and greatly increasing their cost. Using synthetic biology and metabolic engineering, the project will develop new production systems for high value diterpenoids by exploiting recent gene-based discoveries and novel platforms developed by the academic partner laboratories. The aim of this project is to develop scalable heterologous production systems for diterpenoids. First, "chassis organisms" will be constructed that can supply elevated levels of the common diterpenoid precursor geranylgeranyl pyrophosphate. Genes for secondary metabolism will then be introduced into these chassis to create strains producing specific target compounds. We will then scale up laboratory production processes to pilot scale (eg 100 litre fermenter) and develop processes for the purification of the target compounds. Although we will focus primarily on specific diterpenoids of interest to the industrial partners within our consortium, the GGPP producing chassis will be universal in that they could also be adapted to produce a wider range of diterpenoids of interest to the pharmaceutical, personal care, food, fragrance and agricultural industries. The overall team has a very good balance of 'push and pull' and is well placed academically, technically and commercially to deliver a high impact project for the IB Catalyst.

Summary

Plants produce a wide range of diterpenoids, many of which are used commercially such as a paclitaxel, employed in the treatment of cancers, and steviol glyclosides which are used as zero-calorie natural sweeteners. Many other useful diterpenoids cannot yet be commercially exploited due to their limited availability and/or high production costs. Using synthetic biology it is now possible to engineer organisms such as yeast so that they are able to convert simple sugars to high-value chemicals. This project will develop yeast, algae and higher plant species as "chassis organisms" which can be used for the scalable production of diterpenoids. Our project will focus in particular on compounds which could be used in the treatment of cancers, or used in skin products such as sunscreens to protect skin against harmful UV light. These biological production systems will also be useful in producing many other diterpenoids that are found in nature.

Impact Summary

As described in the proposal submitted to TSB.
Committee Research Committee C (Genes, development and STEM approaches to biology)
Research TopicsCrop Science, Industrial Biotechnology, Microbiology, Pharmaceuticals, Plant Science, Synthetic Biology
Research PriorityX – Research Priority information not available
Research Initiative Industrial Biotechnology Catalyst (IBCAT) [2014-2015]
Funding SchemeX – not Funded via a specific Funding Scheme
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