Principles for designing synthetic microbial communities

Abstract

Advances in synthetic biology to build microbes with defined and controllable properties are enabling new approaches to design and program multispecies communities. This emerging field of synthetic ecology will be important for many areas of biotechnology, bioenergy and bioremediation. This endeavor draws upon knowledge from synthetic biology, systems biology, microbial ecology and evolution. Fully realizing the potential of this discipline requires the development of new strategies to control the intercellular interactions, spatiotemporal coordination, robustness, stability and biocontainment of synthetic microbial communities. Here, we review recent experimental, analytical and computational advances to study and build multi-species microbial communities with defined functions and behavior for various applications. We also highlight outstanding challenges and future directions to advance this field.

Figure 1

A summary of the design and utility of synthetic microbial communities. In addition to principles used in single-strain engineering, community engineering allows for diversification of biochemical roles in breaking down complex substrates, and optimized compartmentalization of pathways between individuals for simultaneous execution of multiple functions with reduced individual burden. Synthetic communities can be further engineered with increased robustness through interdependencies and spatiotemporal control.

Figure 2

Key principles for engineering microbial communities. (A) Various metabolic interactions can be designed and leveraged for multispecies production of a desired product. (B) Communities can be spatially and temporally coordinated through engineered environments and programmed aggregation behavior. Quantitative in silico modeling of structured environments will improve the design of these consortia. (C) Population robustness can be maintained through strategies that enhance cooperation, avoid cheating, and promote non-metabolic stabilizing interactions, such as antibiotic antagonism. Various modeling approaches are need to study the dynamics and stability of the systems. (D) Biocontainment methods use synthetic auxotrophies or kill switches to control growth and function of engineered microbial communities.