Scaling Up the Biocatalytic Production of ε-Caprolactam: Advancing Sustainable Lactam Synthesis

Biocatalysis provides a sustainable alternative to conventional chemistry for lactam production from ω-amino acids, using an enzymatic pathway to form amide bond. While this approach grants access to typically poorly functionalized lactams, challenges such as low yields and reaction conditions hinder scalability. In this study, we optimize and scale up an enzymatic lactamization process to 3 L for producing ε-caprolactam from 6-aminohexanoic acid at a titer of 3.9 g/L. This work advances the development of a biocatalytic lactamization method using an ACL (AMP-ligating enzymes and acyl-coenzyme A ligases) enzyme and an ATP regeneration system. Additionally, we present a preliminary investigation into ε-caprolactam purification using membrane-based techniques, including tangential nanofiltration and liquid–liquid extraction via a membrane contactor.