The engineering of spatially linked microbial consortia - potential and perspectives.

Traditional biotechnological applications of microorganisms employ mono-cultivation or co-cultivation in well-mixed vessels disregarding the potential of spatially organized cultures. Metabolic specialization and guided species interactions facilitated through spatial isolation would enable consortia of microbes to accomplish more complex functions than currently possible, for bioproduction as well as biodegradation processes. Here, we review concepts of spatially linked microbial consortia in which spatial arrangement is optimized to increase control and facilitate new species combinations. We highlight that genome-scale metabolic network models can inform the design and tuning of synthetic microbial consortia and suggest that a standardized assembly of such systems allows the combination of 'incompatibles', potentially leading to countless novel applications.

Synthetic Microbial Ecology: Engineering Habitats for Modular Consortia.

The metabolic diversity present in microbial communities enables cooperation toward accomplishing more complex tasks than possible by a single organism. Members of a consortium communicate by exchanging metabolites or signals that allow them to coordinate their activity through division of labor. In contrast with monocultures, evidence suggests that microbial consortia self-organize to form spatial patterns, such as observed in biofilms or in soil aggregates, that enable them to respond to gradient, to improve resource interception and to exchange metabolites more effectively. Current biotechnological applications of microorganisms remain rudimentary, often relying on genetically engineered monocultures (e.g., pharmaceuticals) or mixed-cultures of partially known composition (e.g., wastewater treatment), yet the vast potential of "microbial ecological power" observed in most natural environments, remains largely underused. In line with the Unified Microbiome Initiative (UMI) which aims to "discover and advance tools to understand and harness the capabilities of Earth's microbial ecosystems," we propose in this concept paper to capitalize on ecological insights into the spatial and modular design of interlinked microbial consortia that would overcome limitations of natural systems and attempt to optimize the functionality of the members and the performance of the engineered consortium. The topology of the spatial connections linking the various members and the regulated fluxes of media between those modules, while representing a major engineering challenge, would allow the microbial species to interact. The modularity of such spatially linked microbial consortia (SLMC) could facilitate the design of scalable bioprocesses that can be incorporated as parts of a larger biochemical network. By reducing the need for a compatible growth environment for all species simultaneously, SLMC will dramatically expand the range of possible combinations of microorganisms and their potential applications. We briefly review existing tools to engineer such assemblies and optimize potential benefits resulting from the collective activity of their members. Prospective microbial consortia and proposed spatial configurations will be illustrated and preliminary calculations highlighting the advantages of SLMC over co-cultures will be presented, followed by a discussion of challenges and opportunities for moving forward with some designs.