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13 ERA IB TERPENOSOME: Engineered compartments for monoterpenoid production using synthetic biology

Reference	BB/L027593/1
Principal Investigator / Supervisor	Professor Eriko Takano
Co-Investigators / Co-Supervisors	Professor Nigel Scrutton
Institution	The University of Manchester
Department	Chemistry
Funding type	Research
Value (£)	697,624
Status	Completed
Type	Research Grant
Start date	01/07/2014
End date	31/01/2018
Duration	43 months

Abstract

Terpenoids are commercially valuable natural fine chemicals with a variety of uses as drugs (taxol, artemisinin), nutraceuticals (carotenoids), cosmetics (astaxanthin), and agriculturals (gibberellins). Monoterpenoids are mainly produced in plants and are used as flavours (e.g. limonene), and fragrances (e.g. carveol), as well as precursors for pharmaceutical molecules. However, the natural production of commercially relevant monoterpenes is limited, since their extraction from plants is costly and inefficient, and the alternative chemical synthesis involves long and complex, multi-step protocols. Monoterpenes produced from bacteria using heterologous biosynthesis pathways would be ideal for sustainability and compound diversity; however, so far it has produced low yields, while sesquiterpenes have been successfully overproduced by, e.g., Martin and coworkers (2003, Nature Biotech 21:796-802). TERPENOSOME will develop yeast and bacterial monoterpenoid producing strains using synthetic biology approaches, which bypass many of the production constraints associated with chemical synthesis and isolation from natural resources. Metabolosomes are recently discovered bacterial organelles, which are large structures composed of an exterior protein shell with multiple enzymes compartmentalised on the inside. There are currently only two examples reported in the literature for the localisation of green fluorescent protein inside ethanolamine utilization metabolosomes (Choudhary et al., 2012). These serve as excellent proof-of-concept examples to show: (1) that non-native proteins can be targeted inside metabolosomes, and (2) that metabolosomes can be used as closed scaffolds inside host organisms. TERPENOSOME will be the first to apply the metabolosome to synthetically designed monoterpene biosynthesis for production improvement, side product reduction through improved metabolic control and higher local flux, and to avoid toxicity limiting production levels.

Summary

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Impact Summary

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Committee	Research Committee D (Molecules, cells and industrial biotechnology)
Research Topics	Industrial Biotechnology, Microbiology, Synthetic Biology
Research Priority	X – Research Priority information not available
Research Initiative	ERA Industrial Biotechnology (ERA-IB) [2013-2014]
Funding Scheme	X – not Funded via a specific Funding Scheme

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