Using LanM Enzymes to Modify Glucagon-Like Peptides 1 and 2 in E.coli

Kjeldgaard Larsen, C.; Lindquist, P.; Rosenkilde, M.; Glendorf, T.; Ravn Madsen, A.; Haselmann, K.; Olesen, K.; Bank Kodal, A. L.; Torring, T.

doi:10.1101/2023.03.20.532734

bioRxiv · 10.1101/2023.03.20.532734

Using LanM Enzymes to Modify Glucagon-Like Peptides 1 and 2 in E.coli

Kjeldgaard Larsen, C.·Lindquist, P.·Rosenkilde, M.·Glendorf, T.·Ravn Madsen, A.·Haselmann, K.·Olesen, K.·Bank Kodal, A. L.·Torring, T.

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Abstract

Selective modification of peptides is often exploited to improve pharmaceutically relevant properties of bioactive peptides like stability, circulation time, and potency. In Nature, natural products belonging to the class of ribosomally synthesized and post-translationally modified peptides (RiPPs) are known to install a number of highly attractive modifications with high selectivity. These modifications are installed by enzymes guided to the peptide by corresponding leader peptides removed as the last step of biosynthesis. Here, we exploit leader peptides and their matching enzymes to investigate the installment of D-Ala post-translationally in a critical position in the hormones, glucagon-like peptides (GLP) 1 and 2. We also offer insight into how precursor peptide design can modulate the modification pattern achieved.

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Kjeldgaard Larsen, C., Lindquist, P., Rosenkilde, M., Glendorf, T., Ravn Madsen, A., Haselmann, K., Olesen, K., Bank Kodal, A. L., Torring, T.. 2023-03-20. Using LanM Enzymes to Modify Glucagon-Like Peptides 1 and 2 in E.coli. https://doi.org/10.1101/2023.03.20.532734

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