Synthetic biology has yielded a sophisticated toolbox for engineering single cells. Now, synthetic multi-cellular systems are within reach. This will require a robust and scalable cell-cell signaling language. Available communication systems, such as bacterial quorum sensing components, are inherently limited in their scalability and orthogonality. Yeast and related fungal species secrete peptide pheromones 9-13 residues in length that are sensed by membrane-bound G-protein-coupled receptors (GPCRs) to initiate mating. Therefore, we envisioned that the fungal peptide/GPCR mating language would be an ideal source of orthogonal, readily engineered parts for a scalable synthetic communication language. We have identified and validated several peptide/GPCR pairs for functional activation in yeast.  We tested a subset of the validated peptide/GPCR pairs for functional peptide secretion <i>in vivo, </i>using an engineered secretion vector. With this new tool in hand, we have designed and built several multi-cellular networks. The robustness and scalability of this approach will enable the development of ever more complex multicellular systems. <br/>

Engineering a synthetic peptide/GPCR communication language in yeast

253rd National Meeting (2017)

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