Zhepu Ruan

Engineering natural microbiomes for biotechnological applications remains challenging, as metabolic interactions within microbiomes are largely unknown, and practical principles and tools for microbiome engineering are still lacking. Here, we present a combinatory top-down and bottom-up framework to engineer natural microbiomes for the construction of function-enhanced synthetic microbiomes. We show that application of herbicide and herbicide-degrader inoculation drives a convergent succession of different natural microbiomes toward functional microbiomes (e.g., enhanced bioremediation of herbicide-contaminated soils). We develop a metabolic modeling pipeline, SuperCC, that can be used to document metabolic interactions within microbiomes and to simulate the performances of different microbiomes. Using SuperCC, we construct bioremediation-enhanced synthetic microbiomes based on 18 keystone species identified from natural microbiomes. Our results highlight the importance of metabolic interactions in shaping microbiome functions and provide practical guidance for engineering natural microbiomes.

BACKGROUND: Individual organisms are linked to their communities and ecosystems via metabolic activities. Metabolic exchanges and co-dependencies have long been suggested to have a pivotal role in determining community structure. In phloem-feeding insects such metabolic interactions with bacteria enable complementation of their deprived nutrition. The phloem-feeding whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) harbors an obligatory symbiotic bacterium, as well as varying combinations of facultative symbionts. This well-defined bacterial community in B. tabaci serves here as a case study for a comprehensive and systematic survey of metabolic interactions within the bacterial community and their associations with documented occurrences of bacterial combinations. We first reconstructed the metabolic networks of five common B. tabaci symbionts genera (Portiera, Rickettsia, Hamiltonella, Cardinium and Wolbachia), and then used network analysis approaches to predict: (1) species-specific metabolic capacities in a simulated bacteriocyte-like environment; (2) metabolic capacities of the corresponding species' combinations, and (3) dependencies of each species on different media components. RESULTS: The predictions for metabolic capacities of the symbionts in the host environment were in general agreement with previously reported genome analyses, each focused on the single-species level. The analysis suggests several previously un-reported routes for complementary interactions and estimated the dependency of each symbiont in specific host metabolites. No clear association was detected between metabolic co-dependencies and co-occurrence patterns. CONCLUSIONS: The analysis generated predictions for testable hypotheses of metabolic exchanges and co-dependencies in bacterial communities and by crossing them with co-occurrence profiles, contextualized interaction patterns into a wider ecological perspective.

Microbial communities play vital roles in biogeochemical cycles, allowing biodegradation of a wide range of pollutants. Although many studies have shown the importance of interspecies interactions on activities of communities, fully elucidating the complex interactions in microbial communities is still challenging. Here, we isolated a consortium containing two bacterial strains (Acinetobacter sp. AG3 and Bacillus sp. R45), which could mineralize bromoxynil octanoate (BO) with higher efficiency than either strain individually. The BO degradation pathway by the synergistic consortium was elucidated, and interspecies interactions in the consortium were explored using genome-scale metabolic models (GSMMs). Modeling showed that growth and degradation enhancements were driven by metabolic interactions, such as syntrophic exchanges of small metabolites in the consortium. Besides, nutritional enhancers were predicted to improve BO degradation, which were tested experimentally. Overall, our results will enhance our understanding of microbial mineralization of BO by consortia and promote the application of microbial communities for bioremediation.