http://english.cas.cn/newsroom/research_news/life/202503/t20250321_908532.shtml
https://www.nature.com/articles/s41586-025-08670-3
Researchers from the CAS Tianjin Institute of Industrial Biotechnology, together with collaborators from Hangzhou Normal University, have revealed the catalytic role of reactive oxygen species (ROS) superoxide (O₂•⁻) in a haem-catalase mediated synthesis of ergot alkaloids (EAs).
They found that EasC contains two distinct catalytic “workshops”: one located within the enzyme’s haem pocket, and another on its surface pocket, connected by a slender tunnel. The internal workshop generates superoxide, which is then transported via the tunnel to the surface workshop, where it catalyzes a series of radical reactions that convert substrates into the final EA products. This “dual-workshop with a transport pipeline” enzymatic mechanism is akin to constructing two specialized facilities on a molecular scale—one producing ROS and the other synthesizing EA—while establishing a dedicated transport tunnel for ROS. This spatial segregation and transport strategy harnesses the potent reactivity of ROS while circumventing its destructive potential, showcasing the evolutionary ingenuity of microbial enzyme systems in oxygen chemistry.
Remarkably, the study found that the reduction of O2 for ROS production in the haem pocket, traditionally thought to require external electron donors, is instead directly powered by the substrate here.
While superoxide is typically recognized for its destructive effects on DNA, proteins, and other cellular molecules, this study highlights a novel, constructive role for the molecule in biosynthesis. It underscores nature’s evolutionary ingenuity, revealing that ROS can be strategically employed as catalytic agents in complex biochemical pathways.
