Lawrence Berkeley National Laboratory
Application of an Acyl-CoA Ligase from Streptomyces aizunensis for Lactam Biosynthesis.
- Author(s): Zhang, Jingwei
- Barajas, Jesus F
- Burdu, Mehmet
- Wang, George
- Baidoo, Edward E
- Keasling, Jay D
- et al.
Published Web Locationhttps://doi.org/10.1021/acssynbio.6b00372
ε-Caprolactam and δ-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 ω-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 γ-butyrolactam, 5-aminovaleric acid into δ-valerolactam and 6-aminocaproic acid into ε-caprolactam. Recombinant E. coli expressing ORF26 produced valerolactam and caprolactam when 5-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 δ-valerolactam from lysine.