Collaborative Biosynthesis of Maleimide- and Succinimide-Containing Natural Products by Fungal Polyketide Megasynthases

Fungal polyketide
synthases (PKSs) can function collaboratively
to synthesize natural products of significant structural diversity.
Here we present a new mode of collaboration between a highly reducing
PKS (HRPKS) and a PKS-nonribosomal peptide synthetase (PKS-NRPS) in
the synthesis of oxaleimides from the Penicillium species. The HRPKS is recruited in the synthesis of an olefin-containing
free amino acid, which is activated and incorporated by the adenylation
domain of the PKS-NRPS. The precisely positioned olefin from the unnatural
amino acid is proposed to facilitate a scaffold rearrangement of the
PKS-NRPS product to forge the maleimide and succinimide cores of oxaleimides.