Mixed microbial communities exhibit emergent biochemical properties not found in clonal monocultures. We report a new type of synthetic genetic interaction, synthetic mutualism in trans (SMIT), in which certain pairs of auxotrophic Escherichia coli mutants complement one another's growth by cross-feeding essential metabolites. We find significant metabolic synergy in 17% of 1035 such pairs tested, with SMIT partners identified throughout the metabolic network. Cooperative phenotypes show more growth on average by aiding the proliferation of their conjugate partner, thereby expanding the source of their own essential metabolites. We construct a quantitative, predictive, framework for describing SMIT interactions as governed by stoichiometric models of the metabolic networks of the interacting strains.
Isolated, clonal populations of cells are rarely found in nature. The emergent properties of microbial consortia present a challenge for the systems approach to biology, as chances for competition, communication, or collaboration multiply with the number of interacting agents. This review focuses on recent work on intercourse within biofilms, among quorum-sensing populations, and between cross-feeding metabolic cooperators. New tools from synthetic biology allow microbial interactions to be designed and tightly controlled, creating valuable model systems. We address both natural and synthetic partnerships, with an emphasis on how system behaviors derive from the properties of their components. Essential features of microbial biology arose in the context of a very mixed culture and cannot be understood without unscrambling it.
BackgroundThe engineering of metabolism holds tremendous promise for the production of desirable metabolites, particularly alternative fuels and other highly reduced molecules. Engineering approaches must redirect the transfer of chemical reducing equivalents, preventing these electrons from being lost to general cellular metabolism. This is especially the case for high energy electrons stored in iron-sulfur clusters within proteins, which are readily transferred when two such clusters are brought in close proximity. Iron sulfur proteins therefore require mechanisms to ensure interaction between proper partners, analogous to many signal transduction proteins. While there has been progress in the isolation of engineered metabolic pathways in recent years, the design of insulated electron metabolism circuits in vivo has not been pursued.ResultsHere we show that a synthetic hydrogen-producing electron transfer circuit in Escherichia coli can be insulated from existing cellular metabolism via multiple approaches, in many cases improving the function of the pathway. Our circuit is composed of heterologously expressed [Fe-Fe]-hydrogenase, ferredoxin, and pyruvate-ferredoxin oxidoreductase (PFOR), allowing the production of hydrogen gas to be coupled to the breakdown of glucose. We show that this synthetic pathway can be insulated through the deletion of competing reactions, rational engineering of protein interaction surfaces, direct protein fusion of interacting partners, and co-localization of pathway components on heterologous protein scaffolds.ConclusionsThrough the construction and characterization of a synthetic metabolic circuit in vivo, we demonstrate a novel system that allows for predictable engineering of an insulated electron transfer pathway. The development of this system demonstrates working principles for the optimization of engineered pathways for alternative energy production, as well as for understanding how electron transfer between proteins is controlled.
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