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Oxidative cyclization of prodigiosin by an alkylglycerol monooxygenase-like enzyme

Nature Chemical Biology volume 13, pages 1155–1157 (2017)Cite this article

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Abstract

Prodiginines, which are tripyrrole alkaloids displaying a wide array of bioactivities, occur as linear and cyclic congeners. Identification of an unclustered biosynthetic gene led to the discovery of the enzyme responsible for catalyzing the regiospecific C–H activation and cyclization of prodigiosin to cycloprodigiosin in Pseudoalteromonas rubra. This enzyme is related to alkylglycerol monooxygenase and unrelated to RedG, the Rieske oxygenase that produces cyclized prodiginines in Streptomyces, implying convergent evolution.

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Figure 1: Biosynthesis of prodiginines in P. rubra compared to that in other organisms.
Figure 2: Analysis of prodigiosin cyclization in vivo and in vitro.

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References

  1. Papireddy, K. et al. J. Med. Chem. 54, 5296–5306 (2011).

    Article  CAS  Google Scholar 

  2. Stankovic, N., Senerovic, L., Ilic-Tomic, T., Vasiljevic, B. & Nikodinovic-Runic, J. Appl. Microbiol. Biotechnol. 98, 3841–3858 (2014).

    Article  CAS  Google Scholar 

  3. Williamson, N.R. et al. Future Microbiol. 2, 605–618 (2007).

    Article  CAS  Google Scholar 

  4. Montaner, B. & Pérez-Tomás, R. Life Sci. 68, 2025–2036 (2001).

    Article  CAS  Google Scholar 

  5. Yamamoto, C. et al. Hepatology 30, 894–902 (1999).

    Article  CAS  Google Scholar 

  6. Jones, B.T., Hu, D.X., Savoie, B.M. & Thomson, R.J. J. Nat. Prod. 76, 1937–1945 (2013).

    Article  CAS  Google Scholar 

  7. Lee, J.S. et al. Appl. Environ. Microbiol. 77, 4967–4973 (2011).

    Article  CAS  Google Scholar 

  8. Sydor, P.K. et al. Nat. Chem. 3, 388–392 (2011).

    Article  CAS  Google Scholar 

  9. Salem, S.M. et al. J. Am. Chem. Soc. 136, 4565–4574 (2014).

    Article  CAS  Google Scholar 

  10. Withall, D.M., Haynes, S.W. & Challis, G.L. J. Am. Chem. Soc. 137, 7889–7897 (2015).

    Article  CAS  Google Scholar 

  11. Kimata, S., Izawa, M., Kawasaki, T. & Hayakawa, Y. J Antibiot. (Tokyo) 70, 196–199 (2017).

    Article  CAS  Google Scholar 

  12. Kancharla, P., Lu, W., Salem, S.M., Kelly, J.X. & Reynolds, K.A. J. Org. Chem. 79, 11674–11689 (2014).

    Article  CAS  Google Scholar 

  13. Hu, D.X., Withall, D.M., Challis, G.L. & Thomson, R.J. Chem. Rev. 116, 7818–7853 (2016).

    Article  CAS  Google Scholar 

  14. Williamson, N.R., Fineran, P.C., Leeper, F.J. & Salmond, G.P.C. Nat. Rev. Microbiol. 4, 887–899 (2006).

    Article  CAS  Google Scholar 

  15. Xie, B.-B. et al. J. Bacteriol. 194, 1637–1638 (2012).

    Article  CAS  Google Scholar 

  16. Williamson, N.R. et al. Mol. Microbiol. 56, 971–989 (2005).

    Article  CAS  Google Scholar 

  17. Shanklin, J., Guy, J.E., Mishra, G. & Lindqvist, Y. J. Biol. Chem. 284, 18559–18563 (2009).

    Article  CAS  Google Scholar 

  18. Bai, Y. et al. Nature 524, 252–256 (2015).

    Article  CAS  Google Scholar 

  19. Tang, M.-C., Zou, Y., Watanabe, K., Walsh, C.T. & Tang, Y. Chem. Rev. 117, 5226–5333 (2017).

    Article  CAS  Google Scholar 

  20. Watschinger, K. & Werner, E.R. IUBMB Life 65, 366–372 (2013).

    Article  CAS  Google Scholar 

  21. Watschinger, K. et al. Biochem. J. 443, 279–286 (2012).

    Article  CAS  Google Scholar 

  22. Futai, M. J. Membr. Biol. 15, 15–28 (1974).

    Article  CAS  Google Scholar 

  23. Mayer, M. et al. Pteridines 24, 105–109 (2013).

    Article  Google Scholar 

  24. Chawrai, S.R., Williamson, N.R., Mahendiran, T., Salmond, G.P.C. & Leeper, F.J. Chem. Sci. 3, 447–454 (2012).

    Article  CAS  Google Scholar 

  25. Barry, S.M. & Challis, G.L. ACS Catal. 3, 2362–2370 (2013).

    Article  CAS  Google Scholar 

  26. Johnson, R.E., de Rond, T., Lindsay, V.N.G., Keasling, J.D. & Sarpong, R. Org. Lett. 17, 3474–3477 (2015).

    Article  CAS  Google Scholar 

  27. Dairi, K., Tripathy, S., Attardo, G. & Lavallée, J.-F. Tetrahedr. Lett. 47, 2605–2606 (2006).

    Article  CAS  Google Scholar 

  28. Hillson, N.J., Rosengarten, R.D. & Keasling, J.D. ACS Synth. Biol. 1, 14–21 (2012).

    Article  CAS  Google Scholar 

  29. Wang, P. et al. Microb. Cell Fact. 14, 11 (2015).

    Article  Google Scholar 

  30. Alihosseini, F., Lango, J., Ju, K.-S., Hammock, B.D. & Sun, G. Biotechnol. Prog. 26, 352–360 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Batth, T.S., Keasling, J.D. & Petzold, C.J. Methods Mol. Biol. 944, 237–249 (2012).

    CAS  PubMed  Google Scholar 

  32. Finn, R.D. et al. Nucleic Acids Res. 42, D222–D230 (2014).

    Article  CAS  Google Scholar 

  33. Price, M.N., Dehal, P.S. & Arkin, A.P. Mol. Biol. Evol. 26, 1641–1650 (2009).

    Article  CAS  Google Scholar 

  34. UniProt Consortium. Nucleic Acids Res. 43, D204–D212 (2015).

  35. Letunic, I. & Bork, P. Nucleic Acids Res. 44, W242–W245 (2016).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank A. Deutschbauer for gifting E. coli WM3064. We thank I. Budin, J. Alonso-Gutierrez, M. Thompson, D. Fercher, J. Barajas, C. Eiben, C. Bailey, S. Richardson, M. Brown, M. Garber, S. Nies, C. Meadows, T.S. Lee, L. Katz, and S. Weschler for helpful discussions; E. de Ugarte for work on the graphical abstract; as well as S. Gardner, E. Coyne, and M. Agnitsch for everyday support. This work was supported by ERASynBio (81861: “SynPath”) to J.D.K., the NIGMS (086374) to R.S., and the UC Berkeley SURF Rose Hills fellowship to P.S., as well as the DOE Joint BioEnergy Institute and the DOE Joint Genome Institute, both funded by the US Department of Energy, Office of Science, Office of Biological and Environmental Research, through contract DE-AC02-05CH11231 between Lawrence Berkeley National Laboratory and the US Department of Energy. The publisher, by accepting the article for publication, acknowledges that the United States Government retains a nonexclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes.

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Authors and Affiliations

  1. Department of Chemistry, University of California, Berkeley, California, USA

    Tristan de Rond, Parker Stow, Rebecca E Johnson & Richmond Sarpong

  2. Department of Chemical and Biomolecular Engineering, University of California, Berkeley, California, USA

    Ian Eigl & Jay D Keasling

  3. DOE Joint BioEnergy Institute, Emeryville, California, USA

    Leanne Jade G Chan, Garima Goyal, Edward E K Baidoo, Nathan J Hillson, Christopher J Petzold & Jay D Keasling

  4. Biological Systems and Engineering Division, Lawrence Berkeley National Lab, Berkeley, California, USA

    Leanne Jade G Chan, Garima Goyal, Edward E K Baidoo, Nathan J Hillson, Christopher J Petzold & Jay D Keasling

  5. DOE Joint Genome Institute, Walnut Creek, California, USA

    Nathan J Hillson

  6. Department of Bioengineering and California Institute for Quantitative Biosciences, University of California, Berkeley, California, USA

    Jay D Keasling

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

    Jay D Keasling

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  1. Tristan de Rond
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Contributions

T.d.R., R.E.J., R.S., and J.D.K. conceived of the study. T.d.R., P.S. and I.E. constructed plasmids and performed microbiological manipulations and extractions, R.E.J. performed synthetic organic chemistry. T.d.R., E.E.K.B., and C.J.P. performed analytical chemistry, L.J.G.C. and C.J.P. performed proteomic analysis, and G.G. and N.J.H. PCR amplified and purified DNA fragments. T.d.R. performed bioinformatic analysis. All authors contributed to the manuscript.

Corresponding authors

Correspondence to Tristan de Rond or Jay D Keasling.

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The authors declare no competing financial interests.

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Supplementary Results, Supplementary Tables 1–7, Supplementary Figures 1–14. (PDF 6404 kb)

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de Rond, T., Stow, P., Eigl, I. et al. Oxidative cyclization of prodigiosin by an alkylglycerol monooxygenase-like enzyme. Nat Chem Biol 13, 1155–1157 (2017). https://doi.org/10.1038/nchembio.2471

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