Elsevier

Tetrahedron Letters

Volume 53, Issue 50, 12 December 2012, Pages 6758-6760
Tetrahedron Letters

Biosynthesis of Athmu, a α,γ-hydroxy-β-amino acid of pahayokolides A–B

https://doi.org/10.1016/j.tetlet.2012.09.119Get rights and content

Abstract

Pahayokolides A–B are cyanobacteria derived non-ribosomal peptides which exhibit cytotoxicity against a number of cancer cell lines. The biosynthetic origin of the 3-amino-2,5,7,8-tetrahydroxy-10-methylundecanoic acid (Athmu) moiety has been investigated using stable isotope incorporation experiments. While α-ketoisocaproic acid (α-KIC), α-hydroxyisocaproic acid (α-HIC), and leucine all serve as precursors to Athmu, the feeding of [1-13C] α-KIC results in more than threefold greater 13C enrichment than the other precursors. This result suggests that α-KIC is the immediate precursor which is selected and activated by the adenylation domain of the loading NRPS module and subsequently reduced in a fashion similar to that of the recently identified pathways for cryptophycins A–B, cereulide, and valinomycin.

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Acknowledgments

This work was supported by the National Institute of Environmental Health Sciences (NIEHS) Grant S11 ES11181. We acknowledge the support of the Hollings Marine Laboratory NMR Facility. Commercial equipment or materials are identified in this Letter to specify adequately the experimental procedure. Such identification does not imply recommendation or endorsement by NIST, nor does it imply that the materials or equipment identified are necessarily the best available for the purpose.

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