Microalgae are a promising resource for the producing of oil for with applications ranging from food to human health, cosmetics, green chemistry or biofuels. While some high value-added applications are already in industrial production, improvements are needed for so-called commodity markets (chemicals, fuels). The microalgae considered for these developments belong to some of the most complex and less well-known eukaryotic groups. It is therefore difficult to address this issue with very fragmented knowledge. Small molecules can help us though.
The microalga studied by the
Biogenesis, dynamics and homeostasis of membrane lipids
team of the Cell & Plant Physiology Laboratory is a diatom, Phaeodactylum tricornutum. Diatoms (Figure) are widespread in oceans and fresh waters and are known for their delicate glass structures, made with silica. Phaeodactylum can be cultivated in the laboratory; its genome is known and molecular tools are available for its manipulation. Some genes involved in oil production have already been identified by homology with plants or yeast.
© Antoine Jaussaud, LPCV
To go further, the team's researchers collaborated with the
CMBA (Center for the screening for BioActive Molecules) of the Large Scale Biology Laboratory, in order to screen a collection of more than 1200 small molecules already described for drug activities. The screen was performed using a specific fluorescent probe that identifies molecules capable of triggering oil accumulation inside the diatom cell. Out of the 1200 molecules tested, 40 have been identified, some of which are the active ingredients of drugs that cause a weight gain in humans, which is not illogical! Sign of the consistency of the approach: families of molecules with similar chemical structures are all active; vice versa, among the molecules selected are molecules of very different structures, but known to target the same metabolic pathways.
Thanks to this approach, several potential targets have been revealed. In particular, the team analyzed small molecules that interfere with sterol metabolism. Targeting this pathway, the initial substrate for sterol synthesis accumulates and is diverted toward the synthesis of oil. Among these molecules, an analogue of estrogen hormone, ethynylestradiol (contraceptive pill) is very active (Figure).
Development of oil droplets (in yellow) caused by the presence of ethynylestradiol, a synthetic estrogen.
This study firstly identified small molecules with a direct interest in triggering oil accumulation by algae [1]. The molecules being "annotated" for the targets they aim for in biomedical contexts, this approach allows enlightening new biological pathways in microalgae. The researchers used these data to unravel the role of nitric oxide (NO)
[2], sterol metabolism, and other signaling pathways
[1].
An unexpected result was to observe how sensitive diatoms are to endocrine disruptors, which represents the first demonstration of the impact these compounds may have on oceanic phytoplankton