Promiscuous indolyl vinyl isonitrile synthases in the biogenesis and diversification of hapalindole-type alkaloids
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The hapalindole-type alkaloids naturally show striking late stage diversification of what was believed to be a conserved intermediate, cis-indolyl vinyl isonitrile (1a). Here we demonstrate enzymatically, as well as through applying a synthetic biology approach, that the pathway generating 1a (itself, a potent natural broad‐spectrum antibiotic) is also dramatically flexible. We harness this to enable early stage diversification of the natural product and generation of a wide range of halo-analogues of cis-indolyl vinyl isonitrile. This approach allows the preparatively useful generation of a series of antibiotics with increased lipophilicity over that of the parent antibiotic.
Ittiamornkul , K , Zhu , Q , Gkotsi , D S , Smith , D R M , Hillwig , M , Nightingale , N , Goss , R J M & Liu , X 2015 , ' Promiscuous indolyl vinyl isonitrile synthases in the biogenesis and diversification of hapalindole-type alkaloids ' Chemical Science , vol In press . DOI: 10.1039/C5SC02919H
Copyright 2015 the Authors. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence (http://creativecommons.org/licenses/by-nc/3.0/).
DescriptionThe research leading to these results has received funding from the Department of Chemistry, University of Pittsburgh (to X.L) and the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013/ERC grant agreement no 614779 (to R.J.M.G).
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