Project keywords

Systems Biology, Systems Biotechnology, Energy, Materials, Manufacturing, Sustainability, Sucrose, Renewable, Isoprenoids, Synthetic biology, Metabolic engineering

Project summary

Isoprenoids are a very large class of natural products. Their chemical and structural diversity lends them to a wide variety of industrial applications (e.g. as pharmaceuticals, fuels, rubbers, nutraceuticals, agricultural chemicals, flavours, fragrances, colorants, etc.). We are interested in several industrially-useful isoprenoids. Examples include isoprene, a C5 hydrocarbon that can be polymerised to make synthetic rubber, and various C10 (monoterpene) and C15 (sesquiterpene) hydrocarbons that can be used to produce bio-jet fuel/bio-diesel (and in other applications). Production of these compounds is non-trivial, since they are not naturally made by E. coli and yeast, and some, notably the monoterpenes, are highly toxic.

Isoprenoids are produced by two distinct metabolic pathways: the mevalonate (MVA) pathway present in all higher organisms as well as yeast and the methylerythritol phosphate (MEP) pathway found in many microbes and plastids. We are using synthetic biology engineering approaches to improve carbon flux through both of these pathways for production of industrially-useful isoprenoids. The aim of this program is to increase conversion of bioprocess feedstocks (such as sucrose) into desired end products by whole cell biocatalysts. We have reconstructed synthetic pathways with improved flux in both yeast and E. coli. We are also examining approaches to minimise carbon loss to competing pathways, redirect carbon into the pathways, and scavenge carbon lost to nonspecific reactions. 


Bongers M, Chrysanthopoulos PK, Behrendorff JBYH, Hodson MP, Vickers CE, Nielsen LK (2015) Systems analysis of methylerythritol-phosphate pathway flux in E. coli: insights into the role of oxidative stress and the validity of lycopene as an isoprenoid reporter metabolite. Microbial Cell Factories 14: 193. PMID: 26610700

Brennan TCR, Williams TC, Schulz BL, Palfreyman RW, Krömer JO, Nielsen LK (2015) Evolutionary engineering improves tolerance for replacement jet fuels in Saccharomyces cerevisiae. Appl Environ Microbiol 81: 3316 –3325. PMID: 25746998

Vickers CE, Behrendorff JBYH, Bongers M, Brennan TCR, Bruschi M, Nielsen LK (2015) Production of industrially relevant isoprenoid compounds in engineered microbes. In: Kamm B (ed) Microorganisms in Biorefineries. Series: Microbiology Monographs, vol. 26. Chapter 11: 303-334.

Vickers CE, Bongers M, Liu Q, Delatte T, Bouwmeester H (2014) Metabolic engineering of volatile isoprenoids in plants and microbes. Plant, Cell and Environment, 37 8: 1753-1775. doi:10.1111/pce.12316

Brennan TCR, Kroemer JO, Nielsen LK (2013) Physiological and transcriptional response to d-limonene in Saccharomyces cerevisiae shows changes to the cell wall, not the plasma membrane. Appl Env Microbiol 79: 3590-3600. PMID: 23542628

Behrendorff JBYH, Vickers CE, Chrysanthopoulos P, Nielsen LK (2013) 2,2-Diphenyl-1-picrylhydrazyl as a screening tool for recombinant monoterpene biosynthesis. Microbial Cell Factories 12:76. PMID: 23968454. PMC3847554

Brennan TCR, Turner CD, Kroemer JO, Nielsen LK (2012) Alleviating monoterpene toxicity using a two-phase extractive fermentation for the bioproduction of jet fuel mixtures in Saccharomyces cerevisiae. Biotechnology & Bioengineering 109: 2513-2522. PMID: 22539043

Project contacts

Lead investigator Dr Claudia Vickers, Professor Lars Nielsen
Research group AIBN Systems & Synthetic Biology
Contact email

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