A self-sufficient β-Methylarginine Biosynthetic Pathway in Planctomyces

Abstract

β-Methylamino acids (β-MAAs) enhance the bioactivity of natural products and possess intrinsic pharmacological properties as free amino acids. While the biosynthetic capacity for this class of non-canonical amino acids has been established in certain bacterial lineages such as Gammaproteobacteria and Actinomycetes, other bacterial phyla remain largely unexplored. Here we report the genome-mining guided discovery of a novel biosynthetic gene cluster capable of producing β-methylarginine, from the phylum Planctomycetes. We provide both in vivo and in vitro evidence that Planctomycetes employ a transaminase (PlaA) and a methyltransferase (PlaB) to synthesize this β-MAA. Unlike previously described β-methylarginine biosynthetic pathways, PlaA and PlaB function as a self-sufficient enzyme cascade that operates without the need for additional keto acid and amino acid partners. These findings expand the catalytic repertoire for β-MAAs biosynthesis and establish Planctomycetes as a new source of secondary metabolites discovery.

Keywords: beta-methyl-arginine, PLP-dependent enzyme, genome mining.