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.真菌聚酮合酶（PKSs）可通过协同作用合成结构多样性显著的天然产物。本研究报道了青霉属真菌在合成草酰亚胺类（oxaleimides）化合物过程中，高还原型聚酮合酶（HRPKS）与聚酮合酶-非核糖体肽合成酶（PKS-NRPS）之间的全新协同模式。HRPKS被招募参与合成一种含烯烃的游离氨基酸，该氨基酸随后被PKS-NRPS的腺苷酸化结构域激活并整合至产物中。研究推测，该非天然氨基酸上精确定位的烯烃基团可促进PKS-NRPS产物的骨架重排，进而构建出草酰亚胺类化合物的马来酰亚胺与琥珀酰亚胺核心结构。