Data_Sheet_1_Shared PKS Module in Biosynthesis of Synergistic Laxaphycins.docx

Cyanobacteria produce a wide range of lipopeptides that exhibit potent membrane-disrupting activities. Laxaphycins consist of two families of structurally distinct macrocyclic lipopeptides that act in a synergistic manner to produce antifungal and antiproliferative activities. Laxaphycins are produced by range of cyanobacteria but their biosynthetic origins remain unclear. Here, we identified the biosynthetic pathways responsible for the biosynthesis of the laxaphycins produced by Scytonema hofmannii PCC 7110. We show that these laxaphycins, called scytocyclamides, are produced by this cyanobacterium and are encoded in a single biosynthetic gene cluster with shared polyketide synthase enzymes initiating two distinct non-ribosomal peptide synthetase pathways. The unusual mechanism of shared enzymes synthesizing two distinct types of products may aid future research in identifying and expressing natural product biosynthetic pathways and in expanding the known biosynthetic logic of this important family of natural products.

蓝藻产生多种具有强大膜破坏活性的脂肽。拉克萨菲辛由两种结构上不同的宏环脂肽家族组成，它们以协同作用的方式产生抗真菌和抗增殖活性。拉克萨菲辛由多种蓝藻产生，但其生物合成起源尚不明确。在本研究中，我们确定了由 Scytonema hofmannii PCC 7110 产生的拉克萨菲辛的生物合成途径。我们表明，这些拉克萨菲辛被称为scyto Cyclamides，由这种蓝藻产生，并编码在一个包含共享的多聚酮合成酶的单个生物合成基因簇中，这些酶启动了两个不同的非核糖体肽合成酶途径。这种共享酶合成两种不同类型产物的异常机制可能有助于未来研究识别和表达天然产物生物合成途径，并扩展已知的重要天然产物家族的生物合成逻辑。