A labile point in mutant amphotericin polyketide synthases |
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Authors: | Naseem Khan Bernard Rawlings Patrick Caffrey |
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Institution: | (1) School of Biomolecular and Biomedical Science and Centre for Synthesis and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland;(2) Department of Chemistry, University of Leicester, Leicester, LE1 7RH, UK; |
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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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Keywords: | |
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