TY - JOUR
T1 - Promiscuous indolyl vinyl isonitrile synthases in the biogenesis and diversification of hapalindole-type alkaloids
AU - Ittiamornkul, Kuljira
AU - Zhu, Qin
AU - Gkotsi, Danai Stella
AU - Smith, Duncan Robert Miller
AU - Hillwig, Matthew
AU - Nightingale, Nicole
AU - Goss, Rebecca Jane Miriam
AU - Liu, Xinyu
N1 - The 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).
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://www.rsc.org/suppdata/c5/sc/c5sc02919h/c5sc02919h1.pdf
U2 - 10.1039/C5SC02919H
DO - 10.1039/C5SC02919H
M3 - Article
SN - 2041-6520
VL - In press
JO - Chemical Science
JF - Chemical Science
ER -