Evolution and Impact of Imine Reductases (IREDs) Research: A Knowledge Mapping Approach

Nitrogen-containing compounds, particularly those with chiral amine structures, play a crucial role in the development of organic active pharmaceutical ingredients. Imine reductases (IREDs), NAD(P)H-dependent enzymes that catalyze the reduction of cyclic imines and the reductive amination of prochiral ketones, offer significant industrial potential for the synthesis of chiral amines. However, despite the growing body of research, a comprehensive and unbiased assessment of IRED research remains lacking. This study aims to explore the research landscape and evolution of IREDs using bibliometric and knowledge mapping methods. A total of 239 research articles and reviews on IREDs, published between 2010 and 2024, were retrieved from the Web of Science Core Collection and analyzed using tools such as CiteSpace, VOSviewer, Pajek, and Scimago Graphica. Results showed a consistent increase in both publications and citations, with a sharp rise since 2014. Collaboration network analysis revealed that the United Kingdom leads the field in terms of publications and influential institutions, while ChemCatChem was identified as the journal with the highest number of articles. Nicholas J. Turner emerged as a key researcher, having published the most papers and achieving the second-highest citation frequency. Research trends and keyword analysis highlighted areas of focus such as IRED crystal structure resolution, protein engineering modifications, and expanded industrial applications, including multi-enzyme cascade reactions. Ongoing advancements in synthetic biology, protein modifications, and enzyme engineering are expected to drive further studies on highly active IREDs for asymmetric synthesis of pharmaceutical compounds, positioning this research at the forefront of the field. By employing bibliometric analysis, this study provides the first visual representation of IRED research, offering valuable insights into current trends and emerging topics that will aid scholars in identifying key research areas and potential collaborators.