Prof. Wu’s research primarily focuses on biosynthesis beyond natural evolution.  Synthetic biology are recognized as one of the most influential cutting-edge technologies for the future. However, the current applications of bio-manufacturing remain highly limited, primarily confined to producing natural products—far from meeting the synthesis demands for vast arrays of non-natural chemicals. The fundamental limitation lies in natural enzymes' restricted reaction types, which cannot provide the diverse catalytic modes required for chemical synthesis. Artificially designing enzymes with target catalytic activities to enable bio-manufacturing of more non-natural chemicals holds promise for delivering eco-revolutionary technologies across chemical, pharmaceutical, and materials industries. Our research aims to establish artificial enzyme design technology that integrates chemical catalytic modes with enzymatic characteristics. This involves constructing artificial active centers containing non-natural catalytic groups within enzymes, embedding the rich catalytic paradigms developed in organic chemistry into enzyme active cavities. Subsequent protein design and directed evolution optimize the compatibility between protein structures and non-natural reaction centers, ultimately creating artificial enzymes that surpass natural catalytic mechanisms. Building upon this foundation, we couple artificial enzymes with natural metabolic pathways, evolving them into essential toolkits for biosynthesis. This strategy breaks bottlenecks in non-natural product bio-manufacturing and establishes critical foundational technologies for widespread industrial adoption of green bio-manufacturing. Leveraging artificial enzyme-based synthetic biological systems, we develop novel methods for drug synthesis and targeted delivery, along with biosynthesized novel materials, providing innovative technologies for medical and health applications.