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.

  • Compound

    Prodigiosin

  • Compound

    Cycloprodigiosin

  • Compound

    2-methyl-5-n-amylpyrrole

  • Compound

    4-methoxy-2,2'-bipyrrole-5-carboxaldehyde

  • Compound

    4-hydroxy-2,2'-bipyrrole-5-carboxaldehyde

  • Compound

    Norprodigiosin

  • Compound

    2-methyl-3-butylprodiginine

  • Compound

    2-methyl-3-hexylprodiginine

  • Compound

    2-methyl-3-butylnorprodiginine

  • Compound

    2-methyl-3-hexylnorprodiginine

  • Compound

    2-methyl-3-heptylnorprodiginine

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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.

Author information

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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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.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Tristan de Rond or Jay D Keasling.

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DOI

https://doi.org/10.1038/nchembio.2471