Promiscuous indolyl vinyl isonitrile synthases in the biogenesis and diversification of hapalindole-type alkaloids
| Autor: | Danai S. Gkotsi, Rebecca J. M. Goss, Qin Zhu, Xinyu Liu, Kuljira Ittiamornkul, Matthew L. Hillwig, Duncan R. M. Smith, Nicole Nightingale |
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| Přispěvatelé: | European Research Council, University of St Andrews. School of Chemistry, University of St Andrews. EaSTCHEM, University of St Andrews. Biomedical Sciences Research Complex |
| Rok vydání: | 2015 |
| Předmět: |
Natural product
010405 organic chemistry Stereochemistry NDAS Late stage General Chemistry Biology Diversification (marketing strategy) QD Chemistry 010402 general chemistry 01 natural sciences 0104 chemical sciences Chemistry chemistry.chemical_compound Synthetic biology chemistry Lipophilicity QD Biogenesis |
| Zdroj: | Chemical Science |
| ISSN: | 2041-6539 2041-6520 |
| DOI: | 10.1039/c5sc02919h |
| Popis: | Promiscuous cis-indolyl vinyl isonitrile biosynthetic pathway allowed the preparatively useful generation of nine halosubstituted antibiotic analogues with increased lipophilicity. 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 1a. This approach allows the preparatively useful generation of a series of antibiotics with increased lipophilicity over that of the parent antibiotic. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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