Engineering microbial consortia: a new frontier in synthetic biology

Brenner, Katie; Li, You; Arnold, Frances H.

doi:10.1016/j.tibtech.2008.05.004

Cited by 873 publications

(644 citation statements)

References 58 publications

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“…Although it is clear that cooperation and competition within microbial communities is central to their stability, maintenance, and longevity, there is limited knowledge about the general principles guiding the formation of these intricate systems. Understanding the underlying governing principles that shape a microbial community is key for microbial ecology but is also crucial for engineering synthetic microbiomes for various biotechnological applications (1)(2)(3). Numerous such examples have been recently described including the bioconversion of unprocessed cellulolytic feedstocks into biofuel isobutanol using fungal-bacterial communities (4) and biofuel precursor methyl halides using yeast-bacterial cocultures (5).…”

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confidence: 99%

Syntrophic exchange in synthetic microbial communities

Mee

Collins

Church

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

528

526

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Metabolic crossfeeding is an important process that can broadly shape microbial communities. However, little is known about specific crossfeeding principles that drive the formation and maintenance of individuals within a mixed population. Here, we devised a series of synthetic syntrophic communities to probe the complex interactions underlying metabolic exchange of amino acids. We experimentally analyzed multimember, multidimensional communities of Escherichia coli of increasing sophistication to assess the outcomes of synergistic crossfeeding. We find that biosynthetically costly amino acids including methionine, lysine, isoleucine, arginine, and aromatics, tend to promote stronger cooperative interactions than amino acids that are cheaper to produce. Furthermore, cells that share common intermediates along branching pathways yielded more synergistic growth, but exhibited many instances of both positive and negative epistasis when these interactions scaled to higher dimensions. In more complex communities, we find certain members exhibiting keystone species-like behavior that drastically impact the community dynamics. Based on comparative genomic analysis of >6,000 sequenced bacteria from diverse environments, we present evidence suggesting that amino acid biosynthesis has been broadly optimized to reduce individual metabolic burden in favor of enhanced crossfeeding to support synergistic growth across the biosphere. These results improve our basic understanding of microbial syntrophy while also highlighting the utility and limitations of current modeling approaches to describe the dynamic complexities underlying microbial ecosystems. This work sets the foundation for future endeavors to resolve key questions in microbial ecology and evolution, and presents a platform to develop better and more robust engineered synthetic communities for industrial biotechnology.synthetic ecosystem | amino acid exchange | population modeling M icrobes are abundantly found in almost every part of the world, living in communities that are diverse in many facets. Although it is clear that cooperation and competition within microbial communities is central to their stability, maintenance, and longevity, there is limited knowledge about the general principles guiding the formation of these intricate systems. Understanding the underlying governing principles that shape a microbial community is key for microbial ecology but is also crucial for engineering synthetic microbiomes for various biotechnological applications (1-3). Numerous such examples have been recently described including the bioconversion of unprocessed cellulolytic feedstocks into biofuel isobutanol using fungal-bacterial communities (4) and biofuel precursor methyl halides using yeast-bacterial cocultures (5). Other emerging applications in biosensing and bioremediation against environmental toxins such as arsenic (6) and pathogens such as Pseudomonas aeruginosa and Vibrio cholerae have been demonstrated using engineered quorum-sensing Escherichia coli (7, 8). These ...

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mentioning

confidence: 99%

Syntrophic exchange in synthetic microbial communities

Mee

Collins

Church

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

528

526

View full text Add to dashboard Cite

show abstract

“…The interaction with other species allows microorganisms to occupy environmental niches that would otherwise be closed to them and, depending on the ecological niche occupied, they can show different properties and functions. Mixed cultures have accordingly broader metabolic capabilities and greater robustness to environmental fluctuations than single cultures, characteristics that are attractive for biotechnology 6,7 . However, our knowledge of the physical and metabolic interactions that help microbes to survive and to develop in a complex network is limited.…”

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confidence: 99%

Nutritional stress induces exchange of cell material and energetic coupling between bacterial species

et al. 2015

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Knowledge of the behaviour of bacterial communities is crucial for understanding biogeochemical cycles and developing environmental biotechnology. Here we demonstrate the formation of an artificial consortium between two anaerobic bacteria, Clostridium acetobutylicum (Gram-positive) and Desulfovibrio vulgaris Hildenborough (Gram-negative, sulfate-reducing) in which physical interactions between the two partners induce emergent properties. Molecular and cellular approaches show that tight cell-cell interactions are associated with an exchange of molecules, including proteins, which allows the growth of one partner (D. vulgaris) in spite of the shortage of nutrients. This physical interaction induces changes in expression of two genes encoding enzymes at the pyruvate crossroads, with concomitant changes in the distribution of metabolic fluxes, and allows a substantial increase in hydrogen production without requiring genetic engineering. The stress induced by the shortage of nutrients of D. vulgaris appears to trigger the interaction.

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“…Third, FABMOS-fim can create highly organized communities with distinct phenotypes to divide the effort of synthesizing 'costly' compounds 59,60 or separating incompatible biological processes (for example, nitrogen fixation and photosynthesis 13 ). Creating heterogeneous populations with cells performing different tasks can increase fitness and robustness 61 , result in more efficient use of resources 62 and enable cooperation that is essential for complex behaviours. Because of these benefits, some synthetic biologists have advocated engineering microbial strains that live in communities 59,61 as they commonly do in nature (note: the communities do not have to have different species for them to be beneficial 13,57 ).…”

Section: Discussionmentioning

confidence: 99%

“…Creating heterogeneous populations with cells performing different tasks can increase fitness and robustness 61 , result in more efficient use of resources 62 and enable cooperation that is essential for complex behaviours. Because of these benefits, some synthetic biologists have advocated engineering microbial strains that live in communities 59,61 as they commonly do in nature (note: the communities do not have to have different species for them to be beneficial 13,57 ). The FABMOS-fim system could create these different phenotypes and regulate their ratio, rates of switching and gene expression levels.…”

Section: Discussionmentioning

confidence: 99%

Modulating the frequency and bias of stochastic switching to control phenotypic variation

et al. 2014

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Mechanisms that control cell-to-cell variation in gene expression ('phenotypic variation') can determine a population's growth rate, robustness, adaptability and capacity for complex behaviours. Here we describe a general strategy (termed FABMOS) for tuning the phenotypic variation and mean expression of cell populations by modulating the frequency and bias of stochastic transitions between 'OFF' and 'ON' expression states of a genetic switch. We validated the strategy experimentally using a synthetic fim switch in Escherichia coli. Modulating the frequency of switching can generate a bimodal (low frequency) or a unimodal (high frequency) population distribution with the same mean expression. Modulating the bias as well as the frequency of switching can generate a spectrum of bimodal and unimodal distributions with the same mean expression. This remarkable control over phenotypic variation, which cannot be easily achieved with standard gene regulatory mechanisms, has many potential applications for synthetic biology, engineered microbial ecosystems and experimental evolution.

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Engineering microbial consortia: a new frontier in synthetic biology

Cited by 873 publications

References 58 publications

Syntrophic exchange in synthetic microbial communities

Syntrophic exchange in synthetic microbial communities

Nutritional stress induces exchange of cell material and energetic coupling between bacterial species

Modulating the frequency and bias of stochastic switching to control phenotypic variation

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