Ushimaru Richiro, Zheng Ziyang, Xiong Jin, Mori Takahiro, Abe Ikuro, Guo Yisong, Liu Hung-Wen
Department of Chemistry, The University of Texas at Austin, Austin, TX, USA.
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Nat Catal. 2025 Jul 15. doi: 10.1038/s41929-025-01367-w.
Carbon-sulfur bond-forming reactions in natural product biosynthesis largely involve Lewis acid/base chemistry with relatively few examples catalysed by radical -adenosyl-l-methionine (SAM) enzymes. The latter have been limited to radical-mediated sulfur insertion into carbon-hydrogen bonds with the sulfur atom originating from a sacrificial auxiliary iron-sulfur cluster. Here we show that the radical SAM enzyme AbmM encoded in the albomycin biosynthetic gene cluster catalyses a sulfur-for-oxygen swapping reaction, transforming the furanose ring of cytidine 5'-diphosphate to a thiofuranose moiety that is essential for the antibacterial activity of albomycin δ. Thus, in addition to its canonical function of mediating the reductive cleavage of SAM, the radical SAM catalytic cluster of AbmM appears to play a role in providing the sulfur introduced during the AbmM-catalysed reaction. These discoveries not only establish the origin of the thiofuranose core in albomycin δ but, more importantly, also emphasize the functional diversity of radical SAM catalysis.
天然产物生物合成中碳-硫键形成反应主要涉及路易斯酸/碱化学，由自由基-腺苷甲硫氨酸（SAM）酶催化的例子相对较少。后者仅限于自由基介导的硫插入碳氢键，其中硫原子来源于一个牺牲性辅助铁硫簇。在此，我们表明，白霉素生物合成基因簇中编码的自由基SAM酶AbmM催化硫-氧交换反应，将胞苷5'-二磷酸的呋喃糖环转化为硫代呋喃糖部分，这对白霉素δ的抗菌活性至关重要。因此，除了介导SAM还原裂解的经典功能外，AbmM的自由基SAM催化簇似乎在提供AbmM催化反应过程中引入的硫方面发挥作用。这些发现不仅确定了白霉素δ中硫代呋喃糖核心的来源，更重要的是，还强调了自由基SAM催化的功能多样性。
