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

[摘要] 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 alpha-ketoisocaproic acid (alpha-KIC), alpha-hydroxyisocaproic acid (alpha-HIC), and leucine all serve as precursors to Athmu, the feeding of [1-C-13] alpha-KIC results in more than threefold greater C-13 enrichment than the other precursors. This result suggests that alpha-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. (C) 2012 Elsevier Ltd. All rights reserved.

[发布日期] 2012-12-12

[关键词] Pahayokolide;Biosynthesis;alpha,gamma-Hydroxy-beta-amino acid;alpha-KIC;alpha-HIC