Developing platforms for the production of diterpenoids
Lead Research Organisation:
University of Reading
Department Name: Chemistry
Abstract
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Technical Summary
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.
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.
Planned Impact
As described in proposal submitted to TSB
People |
ORCID iD |
| Geoff Brown (Principal Investigator) |
Publications
Czechowski T
(2022)
Gene discovery and virus-induced gene silencing reveal branched pathways to major classes of bioactive diterpenoids in Euphorbia peplus.
in Proceedings of the National Academy of Sciences of the United States of America
Forestier E
(2021)
Developing a Nicotiana benthamiana transgenic platform for high-value diterpene production and candidate gene evaluation
in Plant Biotechnology Journal
Forestier ECF
(2021)
Engineering Production of a Novel Diterpene Synthase Precursor in Nicotiana benthamiana.
in Frontiers in plant science
King AJ
(2016)
A Cytochrome P450-Mediated Intramolecular Carbon-Carbon Ring Closure in the Biosynthesis of Multidrug-Resistance-Reversing Lathyrane Diterpenoids.
in Chembiochem : a European journal of chemical biology