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Discovery of Arginine Modification Enzyme and Arginine-Derived New Natural Product

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Abstract

Natural products (NPs) derived from diverse living organisms, including plants, animals, fungi, and bacteria, play an important role in presenting novel chemical structures and valuable biological activities. It is crucial to look for new modifying enzymes in order to increase the variety of NPs. We focus on car biosynthetic gene cluster (car BGC) because it encodes enzymes homologous to reported arginine-containing cyclodipeptide synthases (RCDPS) and α-KG dependent enzymes. Utilizing both in vitro assay and in vivo transformation, we found that car BGC is responsible for the biosynthesis of an arginine-derived compound, a relatively rare class from fungi; importantly, the enzymatic modifications on this arginine-derived compound are also elucidated. The structure of the compound is interesting because its backbone comprises the diketopiperazine (DKP) structures, and the ease of modification on the DKP holds promise for future research into new structural motifs and the exploration of diverse bioactivities.

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This item is under embargo until September 15, 2025.