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Engineering microalgae for pharmaceutical production

IOTA Pharmaceuticals Ltd and the University of Greenwich received SPARK funding in 2013 to examine the microalga Dunaliella salina  as a potential production vehicle for nutraceuticals and pharmaceuticals, using 1) an integrated biorefinery approach, centred on producing and processing biomass at scale; and 2) contained approaches, for studying stress-induced production of specific metabolites.

1. Biorefinery approaches

The University of Greenwich has access to large amounts of algal cell paste through the EU-funded D-Factory project which they lead [1]. In preliminary experiments at Greenwich, algal biomass was cultivated and harvested to investigate the production levels of a range of compounds, including nutraceuticals (carotenoids, fatty acids) and the chemical co-product bio-glycerol [2]. Processes for the recovery of these and other high-value chemicals, together with routes for their screening against cancer targets at IOTA [3], were established.

2. Contained approaches

The intention is to use Dunaliella salina for engineering high-level production of certain key metabolites. Small scale, enclosed cultivation systems based on PBR technology were evaluated for this purpose, and conditions established for stress-induced metabolite production. RNA and DNA isolation methodologies, suitable for subsequent transcriptomics, genome sequencing and metabolic pathway reconstruction studies, were also developed which, alongside qRT-PCR and CRISPR/Cas techniques, should provide a robust platform for Dunaliella synthetic biology.

Conclusions

The SPARK project provided catalytic funding to formulate production plans and execute preliminary feasibility experiments. Powered by biorefinery approaches mirrored by smaller-scale contained studies, we now have a platform for new product isolation and analysis from this alga. The background information assembled for this project has been submitted for publication [4].

References

1. The CO2 algae biorefinery: D-Factory KBBE.2013.3.2-02 (2013-2017)

2. Harvey PJ, Abubakar A, Xu Y, Bailey D, Milledge JJ, Swamy RAR, Vieira VV, Harris G, Hoekstra H, 
Goacher P, Crespo J, Reinhardt G, Martinelli L, Pipe R, Schroeder DC, Igl-Schmid N, Kokossis AC, Ben-Amotz A, Persson K (2014) The CO2 microalgae biorefinery: high value products from low value wastes using halophylic microalgae in the D-Factory. Part 1: tackling cell harvesting. doi: 10.5071/22ndEUBCE2014-1CV.4.69

3. Moffat J, Rudolph J & Bailey D (2014) Phenotypic screening in cancer drug discovery - past, present and future. Nat Rev Drug Discov. doi: 10.1038/nrd4366

 

4. Bailey D & Harvey PJ (submitted) From photons to fuels and pharmaceuticals - exploiting the chemical biology of the green alga Dunaliella salina. 

 

Source: Summary SPARK report provided by the project partners

 

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