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

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

Funded Value: £697,624
Funded Period: Jul 14 – Jun 17
Funder: BBSRC
Principal Investigator: Eriko Takano
Research Topic: catalysis & enzymology; metabolic engineering

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.

“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.”

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