The increasing interest of microbial communities as promising biocatalyst is leading an intense effort into the development of computational frameworks assisting the analysis and rational engineering of such complex ecosystems. Here, we critically review the recent computational and model-guided advances in the system-level engineering of microbiome, including both the rational bottom-up and the evolutionary top-down approaches. Furthermore, we highlight modeling and computational methods supporting both engineering paradigms. Finally, we discuss the advantages of combining both strategies into a hybrid top-down/bottom-up (middle-out) strategy to engineer synthetic microbial communities with improved performance and scope.
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