Bacteria produce a wide range of lipopeptides that exhibit membrane-disrupting activities. Laxaphycins are structurally distinct macrocyclic lipopeptides that act together to produce synergistic antifungal and antiproliferative activities. Laxaphycins are produced by range of cyanobacteria but their biosynthetic origins remain unclear. Here we identify 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. To our knowledge, laxaphycins are the first clearly distinct polyketide synthase and non-ribosomal peptide synthetase hybrid natural products with shared branched biosynthesis. The unusual mechanism of shared enzymes synthetizing two distinct types of products may help future research on identifying and expressing natural product biosynthetic pathways and expands the known biosynthetic logic of this important family of natural products.

中文翻译：

---

协同紫杉素生物合成中共享的PKS模块

细菌产生广泛的脂肽，表现出破坏膜的活性。Laxaphycins是结构上不同的大环脂肽，它们共同起作用以产生协同的抗真菌和抗增殖活性。Laxaphycins由一系列蓝细菌产生，但其生物合成起源仍不清楚。在这里，我们确定了负责由霍夫曼氏单胞菌PCC 7110产生的laxaphycins的生物合成的生物合成途径。我们证明了这些laxaphycins（称为scytocyclamides）是由这种蓝细菌产生的，并在单个生物合成基因簇中编码，并且具有共同的聚酮化合物合酶启动两个独特的非核糖体肽合成酶途径。据我们所知，Laxaphycins是第一种明显不同的聚酮化合物合酶和非核糖体肽合成酶杂合天然产物，具有共享的分支生物合成。共享酶合成两种不同类型产品的异常机制可能有助于将来有关鉴定和表达天然产物生物合成途径的研究，并扩展该重要天然产物家族的已知生物合成逻辑。