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

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.

A new era of synthetic biology—microbial community design

“…Despite the challenges mentioned earlier, the computational design of a stable, complete synthetic two [ 17 ] and three-strain microbial consortium has been recently successfully completed [ 35 ]. It is also important to note that there already exist numerous tools to support the in silico design of new pathways, and new toolkits for synthetic design are developed based on the results from ensemble dynamic modelling approach [ 4 ]. This highlights the significant progress made in this field and the promising potential for further advancements [ 33 ].…”

“…In parallel with an increased appreciation of the natural functions of microbial consortia, molecular biology tools have matured in power and precision, giving rise to a nascent interest in the engineering of complex natural communities and the rational design of defined microbial communities from the ‘bottom-up’. Proposed applications for synthetic microbial consortia are broad, including mitigation of human disease [ 1 ], increased crop productivity [ 2 ], and sustainable production of valuable biomolecules [ 3 , 4 ]. Yet, there is a significant gap between the theoretical potential of microbial consortia and examples of their successful implementation on real applications on a larger scale, for example, fermentation, raising valid questions about hype versus deliverables.…”