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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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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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.
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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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