Approaches for completing metabolic networks through metabolite damage and repair discovery

in Current Opinion in Systems Biology (2021), 28

Metabolites are prone to damage, either via enzymatic side reactions, which collectively form the underground metabolism, or via spontaneous chemical reactions. The resulting non-canonical metabolites ... [more ▼]

Metabolites are prone to damage, either via enzymatic side reactions, which collectively form the underground metabolism, or via spontaneous chemical reactions. The resulting non-canonical metabolites that can be toxic, are mended by dedicated “metabolite repair enzymes.” Deficiencies in the latter can cause severe disease in humans, whereas inclusion of repair enzymes in metabolically engineered systems can improve the production yield of value-added chemicals. The metabolite damage and repair loops are typically not yet included in metabolic reconstructions and it is likely that many remain to be discovered. Here, we review strategies and associated challenges for unveiling non-canonical metabolites and metabolite repair enzymes, including systematic approaches based on high-resolution mass spectrometry, metabolome-wide side-activity prediction, as well as high-throughput substrate and phenotypic screens. [less ▲]

Using metabolic networks to resolve ecological properties of microbiomes

in Current Opinion in Systems Biology (2018)

The systematic collection, integration and modelling of high-throughput molecular data (multi-omics) allows the detailed characterisation of microbiomes in situ. Through metabolic trait inference ... [more ▼]

The systematic collection, integration and modelling of high-throughput molecular data (multi-omics) allows the detailed characterisation of microbiomes in situ. Through metabolic trait inference, metabolic network reconstruction and modelling, we are now able to define ecological interactions based on metabolic exchanges, identify keystone genes, functions and species, and resolve ecological niches of constituent microbial populations. The resulting knowledge provides detailed information on ecosystem functioning. However, as microbial communities are dynamic in nature the field needs to move towards the integration of time- and space-resolved multi-omic data along with detailed environmental information to fully harness the power of community- and population-level metabolic network modelling. Such approaches will be fundamental for future targeted management strategies with wide-ranging applications in biotechnology and biomedicine. [less ▲]

How to address cellular heterogeneity by distribution biology

in Current Opinion in Systems Biology (2017), 3

Cellular heterogeneity is an immanent property of biological systems that covers very different aspects of life ranging from genetic diversity to cell-to-cell variability driven by stochastic molecular ... [more ▼]

Cellular heterogeneity is an immanent property of biological systems that covers very different aspects of life ranging from genetic diversity to cell-to-cell variability driven by stochastic molecular interactions, and noise induced cell differentiation. Here, we review recent developments in characterizing cellular heterogeneity by distributions and argue that understanding multicellular life requires the analysis of heterogeneity dy- namics at single cell resolution by integrative approaches that combine methods from non-equilibrium statistical physics, in- formation theory and omics biology. [less ▲]