Enzymatic Synthesis of β-lactam Antibiotics: From Enzyme Dataset Construction to Action Mechanism and Semi-Rational Design.

Abstract

β-lactam Antibiotics (BLA) are characterized by the presence of lactam rings, which are widely used and have a huge market scale. Currently, the production of BLA is primarily achieved through a chemical process, which introduces a large number of toxic compounds, resulting inrelatively high environmental costs. As a part of green chemistry, the enzymatic production of BLA is gaining attention because it is non-toxic and pollution-free. This review focuses on industrial enzymes for BLA biosynthesis, which is critical for understanding the reaction process and addressing the deficiencies of low enzyme stability and activity. In this work, a focused dataset of industrial enzymes involved in BLA biosynthesis was constructed, and the structural characteristics of these enzymes were analyzed based on substrate specificity. Subsequently, eight representative enzyme molecules from the database were selected for detailed analyses, particularly focusing on substrate recognition and action mechanisms. Finally, some suggestions for the semi-rational design of enzymes are put forward given the defects existing in BLA biosynthesis. This review not only partially reveals the structure-function relationship of industrial enzyme molecules used in BLA enzymatic synthesis, but also contributes to the semi-rational design of subsequent enzymes, showing certain theoretical significance and application value.