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

The hapalindole-type alkaloids naturally show striking late stage diversification of what was believed to be a conserved intermediate, -indolyl vinyl isonitrile ( ). Here we demonstrate enzymatically, as well as through applying a synthetic biology approach, that the pathway generating (itself, a po...

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Bibliographic Details
Published in:Chemical science (Cambridge) 2015-01, Vol.6 (12), p.6836-6840
Main Authors: Ittiamornkul, Kuljira, Zhu, Qin, Gkotsi, Danai S, Smith, Duncan R M, Hillwig, Matthew L, Nightingale, Nicole, Goss, Rebecca J M, Liu, Xinyu
Format: Article
Language:English
Subjects:
Alkaloids
Antibiotics
Biology
Chemistry
Harnesses
Lipophilicity
Natural products
Parents
Pathways
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Summary:The hapalindole-type alkaloids naturally show striking late stage diversification of what was believed to be a conserved intermediate, -indolyl vinyl isonitrile ( ). Here we demonstrate enzymatically, as well as through applying a synthetic biology approach, that the pathway generating (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 . This approach allows the preparatively useful generation of a series of antibiotics with increased lipophilicity over that of the parent antibiotic.
ISSN:2041-6520
2041-6539
DOI:10.1039/c5sc02919h