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Browsing by Author "Lin, Julia"

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    EXPANDING THE SCOPE OF RADICAL S-ADENOSYLMETHIONINE ENZYMES THROUGH THE ELUCIDATION OF A NOVEL MODIFICATION

    (2025-04-14) Lin, Julia; Seyedsayamdost, Mohammad R.

    The Radical {S}-adenosylmethionine (RaS) enzyme superfamily catalyzes highly diverse and versatile chemical modifications in all kingdoms of life. One notable subset of this powerful enzyme superfamily installs chemically intriguing and diverse modifications onto Ribosomally synthesized and Post-translationally modified Peptide (RiPP) natural products. These RaS enzyme-modified RiPPs (RaS-RiPPs) contain complex structures and exhibit potent biological activities, thus holding clinical relevance as medicinal chemistry scaffolds and drug progenitors. One bioinformatically predicted RaS-RiPP gene cluster encoded in Nitrosomonas oligotropha, termed RGI after its consensus motif, was explored in this work with the intent of expanding the chemical library of RaS enzyme modifications and identifying a new natural product. This investigation indeed yielded evidence for an unprecedented transformation, the attachment of 5'-thioadenosine through a thioether bond onto a RiPP precursor. This modification expands the chemical space of RiPP natural products and highlights RaS-RiPPs as a source of new biosynthetic and small molecule chemistry.