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Synthetic biology of polyketide synthases

  • Metabolic Engineering and Synthetic Biology - Original Paper
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Complex reduced polyketides represent the largest class of natural products that have applications in medicine, agriculture, and animal health. This structurally diverse class of compounds shares a common methodology of biosynthesis employing modular enzyme systems called polyketide synthases (PKSs). The modules are composed of enzymatic domains that share sequence and functional similarity across all known PKSs. We have used the nomenclature of synthetic biology to classify the enzymatic domains and modules as parts and devices, respectively, and have generated detailed lists of both. In addition, we describe the chassis (hosts) that are used to assemble, express, and engineer the parts and devices to produce polyketides. We describe a recently developed software tool to design PKS system and provide an example of its use. Finally, we provide perspectives of what needs to be accomplished to fully realize the potential that synthetic biology approaches bring to this class of molecules.

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Acknowledgements

This work was supported by the Joint BioEnergy Institute, which is funded by the US Department of Energy (DOE), the Office of Science, Office of Biological and Environmental Research under Contract No. DE-AC02-05CH11231 between DOE and Lawrence Berkeley National Laboratory. The publisher, by accepting the article for publication, acknowledges that the US government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of the manuscript, or allow others to do so, for US government purpose. The authors declare no competing financial interests.

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Author notes

  1. Satoshi Yuzawa and Tyler W. H. Backman contributed equally.

Authors and Affiliations

  1. Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA

    Satoshi Yuzawa, Tyler W. H. Backman & Jay D. Keasling

  2. Joint BioEnergy Institute, Emeryville, CA, 94608, USA

    Satoshi Yuzawa, Tyler W. H. Backman, Jay D. Keasling & Leonard Katz

  3. QB3 Institute, University of California, Berkeley, CA, 94720, USA

    Tyler W. H. Backman, Jay D. Keasling & Leonard Katz

  4. Department of Bioengineering, University of California, Berkeley, CA, 94720, USA

    Jay D. Keasling

  5. Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA, 94720, USA

    Jay D. Keasling

  6. Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Hørsholm, Denmark

    Jay D. Keasling

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  1. Satoshi Yuzawa
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  2. Tyler W. H. Backman
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  3. Jay D. Keasling
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  4. Leonard Katz
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Correspondence to Leonard Katz.

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Yuzawa, S., Backman, T.W.H., Keasling, J.D. et al. Synthetic biology of polyketide synthases. J Ind Microbiol Biotechnol 45, 621–633 (2018). https://doi.org/10.1007/s10295-018-2021-9

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