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Natural strategies for the spatial optimization of metabolism in synthetic biology

Nature Chemical Biology volume 8, pages 527–535 (2012)Cite this article

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Abstract

Metabolism is a highly interconnected web of chemical reactions that power life. Though the stoichiometry of metabolism is well understood, the multidimensional aspects of metabolic regulation in time and space remain difficult to define, model and engineer. Complex metabolic conversions can be performed by multiple species working cooperatively and exchanging metabolites via structured networks of organisms and resources. Within cells, metabolism is spatially regulated via sequestration in subcellular compartments and through the assembly of multienzyme complexes. Metabolic engineering and synthetic biology have had success in engineering metabolism in the first and second dimensions, designing linear metabolic pathways and channeling metabolic flux. More recently, engineering of the third dimension has improved output of engineered pathways through isolation and organization of multicell and multienzyme complexes. This review highlights natural and synthetic examples of three-dimensional metabolism both inter- and intracellularly, offering tools and perspectives for biological design.

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Figure 1: Nested endosymbiosis in the cockroach hindgut.
Figure 2: Microbial assemblages can perform coupled metabolic reactions.
Figure 3: Compartmentalization isolates metabolic pathways in eukaryotic and prokaryotic cells.
Figure 4: Enzyme complexes aid in the breakdown and production of complex molecules.
Figure 5: Electron transfer pathways are optimized through spatial organization.

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Acknowledgements

The authors would like to thank J. Hackstein, Z. Summers, D. Lovley, D. Savage and B. Afonso for the use of images. P.M.B. is supported by fellowships from the Harvard University Center for the Environment and the US National Science Foundation Synthetic Biology Engineering Research Center. P.A.S. acknowledges support from the Radcliffe Institute of Advanced Study, the Wyss Institute for Biologically Inspired Engineering, the Department of Defense Army Research Office and the Department of Energy Advanced Research Projects Agency-Energy.

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  1. Christina M Agapakis and Patrick M Boyle: These authors contributed equally to this work.

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  1. Department of Chemical and Biomolecular Engineering, University of California–Los Angeles, Los Angeles, California, USA

    Christina M Agapakis

  2. Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA

    Patrick M Boyle & Pamela A Silver

  3. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA

    Pamela A Silver

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Agapakis, C., Boyle, P. & Silver, P. Natural strategies for the spatial optimization of metabolism in synthetic biology. Nat Chem Biol 8, 527–535 (2012). https://doi.org/10.1038/nchembio.975

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