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Biotechnology Letters

, Volume 33, Issue 6, pp 1121–1126 | Cite as

A labile point in mutant amphotericin polyketide synthases

  • Naseem Khan
  • Bernard Rawlings
  • Patrick CaffreyEmail author
Original Research Paper

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.

Keywords

Amphotericin B Polyketide synthase Ketoreductase Polyenyl-pyrone 

Notes

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.

Supplementary material

10529_2011_538_MOESM1_ESM.doc (104 kb)
Supplementary material 1 (DOC 104 kb)

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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Naseem Khan
    • 1
  • Bernard Rawlings
    • 2
  • Patrick Caffrey
    • 1
    Email author
  1. 1.School of Biomolecular and Biomedical Science and Centre for Synthesis and Chemical BiologyUniversity College DublinDublin 4Ireland
  2. 2.Department of ChemistryUniversity of LeicesterLeicesterUK

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