Genomics-Driven Discovery of Plantariitin A, a New Lipopeptide in DSM9509.

A significant number of silent biosynthetic gene clusters (BGCs) within the genome remain uncharacterized, representing a valuable opportunity for the discovery of new natural products. In this research, the recombineering system ETh1h2e_yi23, which facilitates recombination in and was developed in our previous study, was used for mining the BGCs of DSM9509. By using this recombineering system, the constitutive promoter was precisely inserted into the genome, resulting in the activation of the silent BGC, which led to the production of a new lipopeptide named plantariitin A. A distinctive characteristic of this lipopeptide is the incorporation of a non-proteinogenic amino acid residue, i.e., amino-1,2,3,6-tetrahydro-2,6-dioxo-4-pyrimidinepropanoic acid (ATDPP), which has not been identified in other natural products. A biological activity assay demonstrated that plantariitin A exhibits anti-inflammatory activity. This study further substantiates the notion that the in situ activation of silent BGCs is a crucial strategy for the discovery of new natural products within the genus . With the increasing availability of genomic data and the development of bioinformatics tools, is poised to emerge as a prominent source for the development of new lipopeptides.