title: Biosynthesis of Athmu, a α,γ-hydroxy-β-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 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 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.
authors.affiliation: Department of Chemistry and Biochemistry, Florida International University, Miami, Florida 33199, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Bearden
authors.forename: Juan C
authors.initials: JC
authors.lastname: Rodriguez
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Rein