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Enzymatic total synthesis of enterocin polyketides

Nature Chemical Biology volume 3, pages 557–558 (2007)Cite this article

Abstract

Polyketides are clinically important natural products that often require elaborate organic syntheses owing to their complex chemical structures. Here we report the multienzyme total synthesis of the Streptomyces maritimus enterocin and wailupemycin bacteriostatic agents in a single reaction vessel from simple benzoate and malonate substrates. To our knowledge, our results represent the first in vitro assembly of a complete type II polyketide synthase enzymatic pathway to natural products.

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Figure 1: HPLC analysis at 254 nm of organic extracts from different reconstituted enc PKS enzyme sets.

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Acknowledgements

We thank C. Khosla (Stanford University) for pHAME2 (RlMatB), T.M. Zabriskie (Oregon State University) for pXY200, P.C. Dorrestein for discussions and experimental assistance, and K.A. Reynolds (Portland State University) for pLH16 (SgFabD) and for HPLC-MS analysis of the prodiginines from EncK. This research was supported by US National Institutes of Health Grant AI47818.

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Authors and Affiliations

  1. Scripps Institution of Oceanograph, University of Arizona, 1703 E. Mabel Street, Tucson, 85721, Arizona, USA

    Qian Cheng & Bradley S Moore

  2. College of Pharmacy, University of Arizona, 1703 E. Mabel Street, Tucson, 85721, Arizona, USA

    Qian Cheng, Longkuan Xiang, Miho Izumikawa & Bradley S Moore

  3. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, 92093, California, USA

    Dario Meluzzi & Bradley S Moore

Authors
  1. Qian Cheng
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  2. Longkuan Xiang
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  3. Miho Izumikawa
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  4. Dario Meluzzi
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  5. Bradley S Moore
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Contributions

Q.C., L.X. and M.I. prepared recombinant proteins, Q.C. performed the biochemical assays and with B.S.M. discussed the results and wrote the paper, and D.M. conducted FT-MS analyses.

Corresponding author

Correspondence to Bradley S Moore.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–3, Supplementary Table 1 and Supplementary Methods (PDF 372 kb)

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Cheng, Q., Xiang, L., Izumikawa, M. et al. Enzymatic total synthesis of enterocin polyketides. Nat Chem Biol 3, 557–558 (2007). https://doi.org/10.1038/nchembio.2007.22

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  • DOI: https://doi.org/10.1038/nchembio.2007.22

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