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Promiscuous indolyl vinyl isonitrile synthases in the biogenesis and diversification of hapalindole-type alkaloids

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Kuljira Ittiamornkul, Qin Zhu, Danai Stella Gkotsi, Duncan Robert Miller Smith, Matthew Hillwig, Nicole Nightingale, Rebecca Jane Miriam Goss, Xinyu Liu

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Abstract

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.

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Original languageEnglish
JournalChemical Science
VolumeIn press
Early online date6 Oct 2015
DOIs
StatePublished - 2015
Scopus citations3

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