Production of a Novel Tetrahydroxynaphthalene (THN) Derivative from Nocardia sp. CS682 by Metabolic Engineering and Its Bioactivities

Abstract

Nargenicin A1 is major secondary metabolite produced by <i>Nocardia</i> sp. CS682, with an effective antibacterial activity against various Gram-positive bacteria. Most <i>Nocardia</i> spp. have metabolic ability to produce compounds of diverse nature, so one-strain-many-compounds (OSMAC) approach can be applied for obtaining versatile compounds from these strains. In this study, we characterized a novel 1, 3, 6, 8-tetrahydroxynaphthalene (THN) derivative by metabolic engineering approach leading to the inactivation of nargenicin A1 biosynthesis. By using genome mining, metabolite profiling, and bioinformatics, the biosynthetic gene cluster and biosynthetic mechanism were elucidated. Further, the antibacterial, anticancer, melanin formation, and UV protective properties for isolated THN compound were performed. The compound did not exhibit significant antibacterial and cytotoxic activities, but it exhibited promising UV protection effects. Thus, metabolic engineering is an effective strategy for discovering novel bioactive molecules.