Production of a Novel Tetrahydroxynaphthalene (THN) Derivative from Nocardia sp. CS682 by Metabolic Engineering and Its Bioactivities
Ravindra Mishra,
Dipesh Dhakal,
Jang Mi Han,
Haet Nim Lim,
Hye Jin Jung,
Tokutaro Yamaguchi,
Jae Kyung Sohng
Affiliations
Ravindra Mishra
Institute of Biomolecule Reconstruction (iBR), Department of Life Science and Biochemical Engineering, Sun Moon University, 70 Sun Moon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460, Korea
Dipesh Dhakal
Institute of Biomolecule Reconstruction (iBR), Department of Life Science and Biochemical Engineering, Sun Moon University, 70 Sun Moon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460, Korea
Jang Mi Han
Institute of Biomolecule Reconstruction (iBR), Department of Life Science and Biochemical Engineering, Sun Moon University, 70 Sun Moon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460, Korea
Haet Nim Lim
Institute of Biomolecule Reconstruction (iBR), Department of Life Science and Biochemical Engineering, Sun Moon University, 70 Sun Moon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460, Korea
Hye Jin Jung
Institute of Biomolecule Reconstruction (iBR), Department of Life Science and Biochemical Engineering, Sun Moon University, 70 Sun Moon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460, Korea
Tokutaro Yamaguchi
Institute of Biomolecule Reconstruction (iBR), Department of Life Science and Biochemical Engineering, Sun Moon University, 70 Sun Moon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460, Korea
Jae Kyung Sohng
Institute of Biomolecule Reconstruction (iBR), Department of Life Science and Biochemical Engineering, Sun Moon University, 70 Sun Moon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460, Korea
Nargenicin A1 is major secondary metabolite produced by Nocardia sp. CS682, with an effective antibacterial activity against various Gram-positive bacteria. Most Nocardia 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.
