Department of Chemistry, University of Prince Edward Island , Charlottetown, PE C1A 4P3, Canada.
J Org Chem. 2018 Feb 16;83(4):1876-1890. doi: 10.1021/acs.joc.7b02823. Epub 2018 Jan 29.
Polyketide synthase (PKS) derived natural products are biosynthesized by head-to-tail addition of acetate and malonate extender units resulting in linear extended-polyketide chains. Despite the well-documented structural diversity associated with PKS-derived natural products, C-C chain branching deviating from the usual linear pattern is relatively rare. Herein, type-II PKS angucyclic natural products containing a hemiaminal functionality were identified and proposed as the parent of a series of C-C-branched analogues. These C-C linked acetate or pyruvate branching units were located at the α-positions on the extended polyketide chains of jadomycins incorporating 3- and 4-aminomethylbenzoic acids. Labeling studies utilizing [1-C]-d-glucose provided mechanistic evidence that the C-C bond formation occurred as a result of a previously unidentified post-PKS processing, additional to the enzymes encoded within the biosynthetic gene cluster. Selected compounds were evaluated in cytotoxic or antimicrobial assays.
聚酮合酶（PKS）衍生的天然产物是通过乙酸和丙二酸盐延伸单元的头对头添加生物合成的，导致线性延伸的聚酮链。尽管与 PKS 衍生的天然产物相关的结构多样性已有充分记录，但偏离通常线性模式的 C-C 链分支相对较少。本文鉴定了含有半亚胺官能团的 II 型 PKS 蒽环天然产物，并将其作为一系列 C-C 分支类似物的母体。这些 C-C 连接的乙酸盐或丙酮酸分支单元位于含有 3-和 4-氨甲基苯甲酸的 jadomycins 的延伸聚酮链的 α-位。利用 [1-C]-d-葡萄糖进行的标记研究提供了机制证据，表明 C-C 键的形成是由于先前未识别的聚酮后加工所致，除了生物合成基因簇内编码的酶之外。选择的化合物在细胞毒性或抗菌测定中进行了评估。
