Programmable cell-cell adhesion in synthetic yeast communities for improved bioproduction

In multicellular systems, engineering-controlled cell-cell adhesion and metabolic interdependence are vital for developing complex functionalities. This study introduces a yeast synthetic toolbox for modular cell-cell adhesion and cocultures, aiming to overcome the limitations of existing approaches that lack genetic specificity and control. First, a model yeast strain 007Δ is created with seven main flocculation and agglutination genes removed, providing a clean background for synthetic adhesion systems. Then, three distinct adhesion pair systems-Strategy 1, Strategy 2.1 and Strategy 2.2-are established involving yeast flocculation and agglutination proteins and yeast surface display systems. In addition, a quantitative assessment is conducted on the adhesive specificity and strength, alongside the capability of synthetic adhesion to generate patterns. Finally, we successfully demonstrate enhanced bioproduction of the high-value food antioxidant, resveratrol, utilizing synthetic cocultures coupled with cell adhesion systems. We anticipate that this toolkit will emerge as a valuable resource for diverse applications in synthetic biology and biomanufacturing.