Application of an Acyl-CoA Ligase from Streptomyces aizunensis for Lactam Biosynthesis

epsilon-Caprolactam and delta-valerolactam are important commodity chemicals used in the manufacture of nylons, with millions of tons produced annually. Biological production of these highly valued chemicals has been limited due to a lack of enzymes that cyclize omega-amino fatty acid precursors to corresponding lactams under ambient conditions. In this study, we demonstrated production of these chemicals using ORF26, an acyl-CoA ligase involved in the biosynthesis of ECO-02301 in Streptomyces aizunensis. This enzyme has a broad substrate spectrum and can cyclize 4-aminobutyric acid into gamma-butyrolactam, 5-aminovaleric acid into delta-valerolactam and 6-aminocaproic acid into e-caprolactam. Recombinant E. coli expressing ORF26 produced valerolactam and caprolactam when S-aminovaleric acid and 6-aminocaproic acid were added to the culture medium. Upon coexpressing ORF26 with a metabolic pathway that produced 5-aminovaleric acid from lysine, we were able to demonstrate production of delta-valerolactam from lysine.