Title:    Thionucleoside formation during biosynthesis of albomycins

Time:    2025-10-28 09:30

Lecturer:  Richiro Ushimaru

Institute for Advanced Study, Kyushu University

Venue:    B311, Zeng Chengkui Building

Abstract：

Albomycin δ2 is a nucleoside natural product that possesses an unusual sulfur-containing furanose core, which is essential for its potent antibiotic activity against clinically important pathogens. Here we show that the radical S-adenosyl-L-methionine (SAM) enzyme AbmM encoded by the albomycin δ2 biosynthetic gene cluster (abm cluster) catalyzes the radical-mediated, oxidative incorporation of sulfur to cytidine 5′- diphosphate (CDP) to afford an intermediate in which the bridging oxygen in the ribofuranose ring is replaced by sulfur. The incorporated sulfur appears to originate from an [Fe-S] cluster bound by AbmM rather than exogenous sulfide supplied in the bulk media. The multifunctional kinase AbmG, also encoded by the abm cluster, then catalyzes a rearrangement of the 4′-hydroxy-4′-thiofuranose intermediate to a 5′- oxo-4′-thiofuranose facilitating entry into the albomycin δ2 biosynthetic pathway. Collectively, this work reveals a new mode of thiosugar biosynthesis that involves radical-mediated C–S bond formation distinct from all previously reported mechanisms.

Bio of the Lecturer：

Richiro Ushimaru is an Associate Professor at the Institute for Advanced Study, Kyushu University.Richiro Ushimaru received his Ph.D. in Chemistry from The University of Texas at Austin in 2019 under the supervision of Prof. Hung-wen Liu. After serving as an Assistant Professor at the Graduate School of Pharmaceutical Sciences, The University of Tokyo (2020–2025), he joined Kyushu University as an Associate Professor under the Inamori Frontier Program. His research focuses on the discovery and mechanistic elucidation of novel enzymes in natural product biosynthesis, especially those involved in unusual C–S bond formation, heteroatom insertion, and complex structural modifications. By integrating bioorganic chemistry, enzymology, and synthetic biology, his group aims to uncover new biocatalytic pathways and to create useful bioactive molecules for drug discovery.