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The evolving interface between synthetic biology and functional metagenomics

Abstract

Nature is a diverse and rich source of bioactive pathways or novel building blocks for synthetic biology. In this Perspective, we describe the emerging research field in which metagenomes are functionally interrogated using synthetic biology. This approach substantially expands the set of identified biological activities and building blocks. In reviewing this field, we find that its potential for new biological discovery is dramatically increasing. Functional metagenomic mining using genetic circuits has led to the discovery of novel bioactivity such as amidases, NF-κB modulators, naphthalene degrading enzymes, cellulases, lipases and transporters. Using these genetic circuits as a template, improvements are made by designing biosensors, such as in vitro–evolved riboswitches and computationally redesigned transcription factors. Thus, powered by the rapidly expanding repertoire of biosensors and streamlined processes for automated genetic circuit design, a greater variety of complex selection circuits can be built, with resulting impacts on drug discovery and industrial biotechnology.

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Fig. 1: Construction of a metagenomic library from sample to sequence.
Fig. 2: Genetic circuits used to mine metagenomic libraries.
Fig. 3: Expanding the range of compounds that can be detected using biosensors.
Fig. 4: Genetic circuit design using Cello.11

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Acknowledgements

This research was funded by the Novo Nordisk Foundation and the European Union Seventh Framework Programme (FP7-KBBE-2013-7-single-stage) under grant agreement no. 613745, Promys. M.O.A.S. acknowledges additional funding from The Lundbeck Foundation. E.v.d.H. acknowledges funding from the EU FP7- People-2012-ITN BacTory (317058).

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Correspondence to Morten O. A. Sommer.

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H.J.G. and M.O.A.S. are co-founders of Biosyntia, with commercial interest in the topic of the Perspective.

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van der Helm, E., Genee, H.J. & Sommer, M.O.A. The evolving interface between synthetic biology and functional metagenomics. Nat Chem Biol 14, 752–759 (2018). https://doi.org/10.1038/s41589-018-0100-x

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