A molecular toolkit of cross-feeding strains for engineering synthetic yeast communities.

Rodrigo Ledesma-Amaro, Wei Jiang, Hao-Hong Chen, Alexander P S Darlington, Huadong Peng, Eric J South

Journal: Nature microbiology 2024;9(3):848-863

PMID: 38326570

Abstract

Engineered microbial consortia often have enhanced system performance and robustness compared with single-strain biomanufacturing production platforms. However, few tools are available for generating co-cultures of the model and key industrial host Saccharomyces cerevisiae. Here we engineer auxotrophic and overexpression yeast strains that can be used to create co-cultures through exchange of essential metabolites. Using these strains as modules, we engineered two- and three-member consortia using different cross-feeding architectures. Through a combination of ensemble modelling and experimentation, we explored how cellular (for example, metabolite production strength) and environmental (for example, initial population ratio, population density and extracellular supplementation) factors govern population dynamics in these systems. We tested the use of the toolkit in a division of labour biomanufacturing case study and show that it enables enhanced and tuneable antioxidant resveratrol production. We expect this toolkit to become a useful resource for a variety of applications in synthetic ecology and biomanufacturing.

© 2024. The Author(s).

Address: Department of Bioengineering, Imperial College London, London, UK.; Imperial College Centre for Synthetic Biology, Imperial College London, London, UK.; The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark.; Warwick Integrative Synthetic Biology Centre, School of Engineering, University of Warwick, Coventry, UK.; Molecular Biology, Cell Biology and Biochemistry Program, Boston University, Boston, MA, USA.; Department of Bioengineering, Imperial College London, London, UK.; Imperial College Centre for Synthetic Biology, Imperial College London, London, UK.; School of Food Science and Engineering, South China University of Technology, Guangzhou, China.; Department of Bioengineering, Imperial College London, London, UK. [email protected].; Imperial College Centre for Synthetic Biology, Imperial College London, London, UK. [email protected].

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