Chemical Biology of Microbe-Host Interactions, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI), Beutenbergstraße 11a, 07745, Jena, Germany.
Life Sciences Addition, University of California, Berkeley, Berkeley, CA 94720, USA.
Angew Chem Int Ed Engl. 2022 Oct 10;61(41):e202209105. doi: 10.1002/anie.202209105. Epub 2022 Sep 5.
The choanoflagellate Salpingoeca rosetta is an important model system to study the evolution of multicellularity. In this study we developed a new, modular, and scalable synthesis of sulfonolipid IOR-1A (six steps, 27 % overall yield), which acts as bacterial inhibitor of rosette formation in S. rosetta. The synthesis features a decarboxylative cross-coupling reaction of a sulfonic acid-containing tartaric acid derivative with alkyl zinc reagents. Synthesis of 15 modified IOR-1A derivatives, including fluorescent and photoaffinity-based probes, allowed quantification of IOR-1A, localization studies within S. rosetta cells, and evaluation of structure-activity relations. In a proof of concept study, an inhibitory bifunctional probe was employed in proteomic profiling studies, which allowed to deduce binding partners in bacteria and S. rosetta. These results showcase the power of synthetic chemistry to decipher the biochemical basis of cell differentiation processes within S. rosetta.
玫瑰旋口虫（Salpingoeca rosetta）是研究多细胞生物进化的重要模式生物系统。在这项研究中，我们开发了一种新的、模块化和可扩展的磺基脂 IOR-1A 合成方法（六步反应，总产率为 27%），IOR-1A 可以作为细菌抑制剂来抑制玫瑰旋口虫的细胞形成。该合成方法的特点是羧酸磺酸基酒石酸衍生物与烷基锌试剂的脱羧交叉偶联反应。我们合成了 15 种 IOR-1A 修饰衍生物，包括荧光和光亲和探针，用于定量 IOR-1A、在玫瑰旋口虫细胞内的定位研究，以及评估结构-活性关系。在一个概念验证研究中，我们使用了一种抑制双功能探针进行蛋白质组学分析，这使我们能够推断出与细菌和玫瑰旋口虫结合的伴侣蛋白。这些结果展示了合成化学在破译玫瑰旋口虫细胞分化过程中生化基础的强大功能。
