Over half of all biologically active peptides and peptide hormones are α-amidated at their C-terminus, which is essential for their full biological activities. Amidation is accomplished through the sequential reaction of the two enzymes encoded by the single bifunctional, peptidylglycine α-amidating monooxygenase (PAM or an α-amidating enzyme). PAM catalyzes the formation of a peptide amide from peptide precursors that include a C-terminal glycine, and requires copper, molecular oxygen, and ascorbate. PAM is the only enzyme that produces peptide amides in vivo. However, various strategies utilizing PAM, carboxypeptidase-Y enzymes, and chemical synthesis have been developed for producing peptide amides in vitro. The growing need and importance of peptide amide drugs has highlighted the necessity for an efficient in vitro amidating system for industrial application. In recent years, recombinant systems for enzymatic amidation have received growing attention for the production of peptide hormones, like calcitonin and oxytocin. This review presents the current situation regarding amidation, with a special emphasis on the industrial production of peptide hormones.
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Acknowledgements This work was supported, in part, by the Korea Science and Engineering Foundation (KOSEF) through the Bioproducts Research Center (BRC) at Yonsei University, Technology Business Incubation (TBI) fund, and a Clean Technology Grant from the Korean Ministry of Commerce, Industry and Energy.
All Science Journal Classification (ASJC) codes
- Applied Microbiology and Biotechnology
- Biomedical Engineering