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A labile point in mutant amphotericin polyketide synthases

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Abstract

Streptomyces nodosus produces the antifungal polyene amphotericin B. Numerous modifications of the amphotericin polyketide synthase have yielded new analogues. However, previous inactivation of the ketoreductase in module 10 resulted in biosynthesis of truncated polyketides. Here we show that modules downstream of this domain remain intact. Therefore, loss of ketoreductase-10 activity is sufficient to cause early chain termination. This modification creates a labile point in cycle 11 of the polyketide biosynthetic pathway. Non-extendable intermediates are released to accumulate as polyenyl-pyrones.

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Acknowledgments

NK received a PhD studentship from the Irish Higher Education Authority Programme for Research in Third Level Institutions. PC received the financial support of Science Foundation Ireland under Grant number 09/RFP/GEN2132.

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Authors and Affiliations

  1. School of Biomolecular and Biomedical Science and Centre for Synthesis and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland

    Naseem Khan & Patrick Caffrey

  2. Department of Chemistry, University of Leicester, Leicester, LE1 7RH, UK

    Bernard Rawlings

Authors
  1. Naseem Khan
  2. Bernard Rawlings
  3. Patrick Caffrey

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Correspondence toPatrick Caffrey.

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Khan, N., Rawlings, B. & Caffrey, P. A labile point in mutant amphotericin polyketide synthases.Biotechnol Lett33, 1121–1126 (2011). https://doi.org/10.1007/s10529-011-0538-3

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