In an article published today in the journal Science, Camille Delebecque and Ariel Lindner (INSERM U1001, Centre de Recherches Interdisciplinaires, Faculté de Médecine Paris Descartes) in collaboration with Faisal Aldaye and Pamela Silver at Harvard Medical School broaden the toolbox of synthetic biology. By translating in vivo the principles of DNA nanotechnology, the team developed a new technology enabling to spatially control enzymes within living cells.



This project is part of Camille Delebecque PhD thesis in the Frontiers of Life Sciences ("Frontières du Vivant") Liliane Bettencout PhD program. (ED 474, dir François Taddei)

The ability to spatially control localization of enzymes within cells is of big interest for synthetic biology - the science that deals with engineering microorganisms to produce interesting compounds for humans. Clustering into micro-compartiments or onto scaffolds helps direct substrate flow in-between interacting proteins, limits cross-talk between signaling pathways, and generally increases specificity and yields of sequential metabolic reactions.

To achieve de novo modular control over spatial organization, the researchers borrowed and applied to biology a number of principles from DNA nanotech field. Bacteria were engineered to produce non-coding RNA designed to assemble and polymerize into large structures within cells. These structures were then used as docking sites for proteins involved in a synthetic bio-hydrogen pathway. A high increase in yield was observed as a function of scaffold geometries. Interestingly, this is also a totally modular system potentially applicable to other pathways.

This invention takes us one step closer to the idea of "synthetic organelles" and to the possibility of engineering microorganisms to help us reach sustainable goals. This new level of control in synthetic biology also opens the door to studying more fundamental research questions and new applications in medicine.

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