Microbial Consortia Engineering for Cellular Factories: in vitro to in silico systems

Abstract

This mini-review discusses the current state of experimental and computational microbial consortia engineering with a focus on cellular factories. A discussion of promising ecological theories central to community resource usage is presented to facilitate interpretation of consortial designs. Recent case studies exemplifying different resource usage motifs and consortial assembly templates are presented. The review also highlights in silico approaches to design and to analyze consortia with an emphasis on stoichiometric modeling methods. The discipline of microbial consortia engineering possesses a widely accepted potential to generate highly novel and effective bio-catalysts for applications from biofuels to specialty chemicals to enhanced mineral recovery.

Figure 1

Illustrated examples of microbial consortia organized by common interaction motifs. A) A form of mutualism by microenvironment manipulation where one population has the ability to attach to surfaces and create an environment in which a mutaulistic, non-biofilm forming strain can coexist and help support growth of system. For the example presented in Brenner et al 2011, this is accomplished via quorum sensing with synthetic cocultures. B) An example of consortial co-fermentation of hexose and pentose sugars which highlights synergy by division of resources. C) An example of syntrophic cross-feeding in synthetic auxotrophic cocultures. D) Oxygen consumption by Escherichia coli (blue) aids exoelectrogenic activity of Geobacter sulfurreducens (orange) by creating an anoxic environment. This is an example of commensalism by environment manipulation. E) An applied example of syntrophy by cross-feeding coupled with organic acid detoxification.

Figure 2

Illustrated examples of engineered consortia categorized as A) artificial, B) synthetic and C) semi-synthetic systems. Artificial communities are composed of wild-type populations which do not coexist naturally. Synthetic microbial communities are composed of two or more metabolically engineered cell populations. Semi-synthetic communities combine metabolically engineered cells with wild-type populations. Illustrations are drawn from cited literature examples; A) Ren et al 2007, B) Bernstein et al 2012 and C) Ducat et al 2012.

Figure 3

Illustrated diagram representing three computational methods utilized in community elementary flux mode analysis (cEFMA) from Taffs et al 2009. The dotted red lines indicate system boundaries for simulations where the interior is constrained by steady-state assumptions and the exteriors account for metabolic sources and sinks. The strategies are categorized as A) compartmentalized method in which reactions and metabolites are partitioned into specific species and metabolites can be exchanged through a mass balanced extracellular compartment, B) pooled method which combines all ecosystem relevant reactions and metabolites into a single network model without assignment to specific species and C) nested method which first computes and identifies ecologically relevant results for individual species-level models and then uses these results to perform a second, community-level simulation.