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New PROMICON paper: Understanding the computational and model-guided advances in the system-level engineering of microbiome

26 October 2022
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A new PROMICON-supported research article titled “Toward merging bottom–up and top–down model-based designing of synthetic microbial communities” has been recently published in the Current Opinion in Microbiology journal. The study investigates 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. Being a collaboration between PROMICON and the SynBio4Flav and MixUp projects, the research has been conducted by partners David San León and Joan Nogales from the Spanish National Research Council (CSIC).

Microbial communities are defined as the set of co-occurring, and potentially interacting, microbes present in a defined habitat in space and time. The increasing interest of microbial communities as promising biocatalysts is leading an intense effort into the development of computational frameworks assisting the analysis and rational engineering of such complex ecosystems. The paper looks into system-level microbial-community engineering with a focus on biotechnological applications and addresses rational, bottom-up and evolutionary, top-down approaches, describing how modeling and computational methods are increasingly supporting both engineering paradigms. Finally, it discusses the advantages and convenience of combining both strategies into a hybrid top-down/bottom-up (middle-out) strategy to deliver improved performance.

The main conclusion reached in this paper are the following:

  • Analysis and designing of microbiomes have become a new paradigm in microbiology.
  • Understanding and rational engineering of microbiomes require model-based frameworks.
  • Computational bottom-up and top-down designing lead to superior synthetic microbiomes.
  • New middle-out approaches will provide synthetic communities with high performance.


You can read the full paper here.


Photo: Details of engineering synthetic interspecific relationships (left) and DOL modeling (right) in SMC design with bottom-up approach. The relationships between consortia members can be inferred from (a) previous knowledge stored in metabolic databases and literature legacy, (b) using model contextualization of OMICs, or (c) the use of GEMs. The main designing strategies addressing DOL include (d) cofeeding, (e) network splitting, and (f) distributed catalysis. Key tools and applications are indicated.