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Exploiting plug-and-play synthetic biology for drug discovery and production in microorganisms

Nature Reviews Microbiology volume 9, pages 131–137 (2011)Cite this article

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Abstract

One of the most promising applications of synthetic biology is the biosynthesis of new drugs from secondary metabolites. Here, we survey a wide range of strategies that control the activity of biosynthetic modules in the cell in space and time, and illustrate how these strategies can be used to design efficient cellular synthetic production systems. Re-engineered versions of secondary metabolite biosynthetic pathways identified from any genomic sequence can then be inserted into these systems in a plug-and-play fashion.

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Figure 1: Pipeline for plug-and-play expression of unknown biosynthetic pathways.
Figure 2: Controlling space and time on different scales in an optimized plug-and-play system.

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Acknowledgements

We thank D. Hopwood and C. Voigt for constructive comments and suggestions. This work was supported by the Dutch Technology Foundation (STW), which is the applied-science division of The Netherlands Organisation for Scientific Research (NWO) and the Technology Programme of the Ministry of Economic Affairs (grant STW 10463). R.B. is supported by an NWO–Vidi fellowship, and E.T. is supported by a Rosalind Franklin Fellowship, University of Groningen, the Netherlands.

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Authors and Affiliations

  1. Marnix H. Medema is at the Department of Microbial Physiology and the Groningen Bioinformatics Centre, University of Groningen, Nijenborgh 7, 9747AG Groningen, The Netherlands.,

    Marnix H. Medema

  2. Rainer Breitling is at the Groningen Bioinformatics Centre, University of Groningen, Nijenborgh 7, 9747AG Groningen, The Netherlands, and at the Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, UK.,

    Rainer Breitling

  3. Roel Bovenberg is at the Centre for Synthetic Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747AG Groningen, The Netherlands, and at the DSM Biotechnology Center, Alexander Fleminglaan 1, 2613AX Delft, The Netherlands.,

    Roel Bovenberg

  4. Eriko Takano is at the Department of Microbial Physiology, University of Groningen, Nijenborgh 7, 9747AG Groningen, The Netherlands.,

    Eriko Takano

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Correspondence to Eriko Takano.

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Competing interests

Roel Bovenberg works for DSM, where he is involved in the anti-infectives business.

Marnix H. Medema, Rainer Breitling and Eriko Takano declare no competing financial interest.

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Glossary

Metabolic flux

The flow of metabolites through a metabolic system.

Modularity

The extent to which a system can be subdivided into 'modules' that can be recombined in new ways.

Non-ribosomal-peptide synthetase

A large multidomain megasynthase enzyme that functions as an assembly line to produce peptides, usually containing non-proteinogenic amino acids.

Orthogonal

Functioning entirely uncoupled from the native system, without crosstalk.

Quorum sensing

Intercellular communication between members of a microbial colony or community, carried out through small signalling molecules.

Secondary metabolite

A metabolite that is characteristic of particular strains or species and that has a specific function outside the primary metabolism that governs core cellular functions.

Tailoring enzyme

An enzyme that modifies the core scaffold of a compound by, for example, oxidoreduction, methylation or glycosylation.

Type I modular PKS

A large multidomain megasynthase enzyme that functions as an assembly line to produce a polyketide.

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Medema, M., Breitling, R., Bovenberg, R. et al. Exploiting plug-and-play synthetic biology for drug discovery and production in microorganisms. Nat Rev Microbiol 9, 131–137 (2011). https://doi.org/10.1038/nrmicro2478

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