Abstract

Microbiomes are complex and ubiquitous networks of microorganisms whose seemingly limitless chemical transformations could be harnessed to benefit agriculture, medicine, and biotechnology. The spatial and temporal changes in microbiome composition and function are influenced by a multitude of molecular and ecological factors. This complexity yields both versatility and challenges in designing synthetic microbiomes and perturbing natural microbiomes in controlled, predictable ways. In this review, we describe factors that give rise to emergent spatial and temporal microbiome properties and the meta-omics and computational modeling tools that can be used to understand microbiomes at the cellular and system levels. We also describe strategies for designing and engineering microbiomes to enhance or build novel functions. Throughout the review, we discuss key knowledge and technology gaps for elucidating the networks and deciphering key control points for microbiome engineering, and highlight examples where multiple omics and modeling approaches can be integrated to address these gaps.

Highlights

  • Microbiome functions are driven by myriad abiotic and biotic forces that span multiple length scales and timescales (Figure 1)

  • To gain a predictive understanding of how microbial interaction networks are shaped by environmental stimuli and combine to generate community-level properties, we must consider the molecular mechanism of interactions as well as how they change as a function of time and spatial proximity

  • Linking microbiome composition and function is facilitated by integrating multiple meta-omics techniques, for example, concurrent shotgun metagenomics, metaproteomics, and metabolomics studies to assess which enzymes are producing an observed small molecule of interest and which microbes could produce those enzymes

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Summary

Integrating Systems and Synthetic Biology to Understand and Engineer Microbiomes

Synthetic biology, genetic engineering, computational modeling, meta-omics, microbial interaction network

MICROBOMES OPERATE ON MANY SPATIAL AND TEMPORAL SCALES
Secretion systems facilitate horizontal gene transfer and effector secretion
Microbial Interactions Determine Microbiome Behavior and Stability
Spatial Organization and Biofilms Are Key Properties of Microbiome Resilience
MEMBRANE PROTEINS
Investigating and Designing Microbiomes from the Bottom Up and Top Down
TOOLS FOR UNDERSTANDING MICROBIOMES
Flux measurements require metabolic models
Quantifying Microbiome Composition and Functional Potential via Metagenomics
Using Metatranscriptomics to Map Organism Identities to Functional Activities
National Bioscience Database Center
JGI PhycoCosm JGI Phytozome
Predicts canonical signal peptides in protein sequences
Quantifying Microbiome Functional Capabilities via Metaproteomics
Metabolomics Reveals the Chemical Repertoire of Microbiomes
Investigating Metabolic Flux in Microbial Communities
Stable Isotope Probing in Microbiomes
COMPUTATIONAL MODELS TO PREDICT MICROBIOME DYNAMICS AND FUNCTIONS
Agents Chemical fields
Dynamic Models of Microbiome Flux
ENGINEERING MICROBIOMES
Microbiome Functions Can Be Modified by External Inputs
Laboratory evolution
Rewiring Microbial Functions by Genetic Engineering and Laboratory Evolution
CONCLUSION AND PERSPECTIVES
Findings
LITERATURE CITED
Full Text
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