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Biosynthesis of Athmu, a ?,?-hydroxy-?-amino acid of pahayokolides A-B.

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

SUBMITTER: Liu L

PROVIDER: S-EPMC3500633 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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

Liu Li L Bearden Daniel W DW Rodriguez Juan C JC Rein Kathleen S KS

Tetrahedron letters 20121201 50

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-(13)C] α-KIC results in more than threefold greater (13)C enric ...[more]

PMID: 23172981

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