Characterizing the Biochemical Role of an Unusual Fatty Acyl-AMP Ligase from a Hybrid PKS-NRPS Pathway in Nematodes.

ABSTRACT: PKAL-1 is a fatty acyl-AMP ligase that plays an essential role in the biosynthesis of the nemamides, hybrid polyketide-nonribosomal peptides from nematodes that promote recovery from starvation-induced larval arrest. This enzyme traffics biosynthetic intermediates between two enzymatic assembly lines: the hybrid polyketide synthase-nonribosomal peptide synthetase PKS-1 and the nonribosomal peptide synthetase NRPS-1. Specifically, a pkal-1 mutant worm strain does not produce the nemamides but accumulates a β-amino-containing polyketide, named nematide A, which is made by PKS-1 and is potentially loaded by PKAL-1 onto NRPS-1. Here, however, we show that PKAL-1 does not accept β-amino-containing substrates. Furthermore, phylogenetic and structural analyses of PKAL-1 indicate that it is

SUBMITTER: Gordon MT 

PROVIDER: S-EPMC12487726 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature