Issue 12, 2015
From the journal:

Chemical Science

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

Kuljira Ittiamornkul,a   Qin Zhu,a   Danai S. Gkotsi,b   Duncan R. M. Smith,b   Matthew L. Hillwig,a   Nicole Nightingale,a   Rebecca J. M. Gossb  and  Xinyu Liu*a  

* Corresponding authors

a Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, PA, USA 15260
E-mail: xinyuliu@pitt.edu
Tel: +1-412-624-6932

b School of Chemistry and BSRC, University of St. Andrews, St. Andrews, U.K

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 1a. This approach allows the preparatively useful generation of a series of antibiotics with increased lipophilicity over that of the parent antibiotic.

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

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Article information

DOI
https://doi.org/10.1039/C5SC02919H
Article type
Edge Article
Submitted
07 Aug 2015
Accepted
03 Oct 2015
First published
06 Oct 2015
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2015,6, 6836-6840

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

K. Ittiamornkul, Q. Zhu, D. S. Gkotsi, D. R. M. Smith, M. L. Hillwig, N. Nightingale, R. J. M. Goss and X. Liu, Chem. Sci., 2015, 6, 6836 DOI: 10.1039/C5SC02919H

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