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.
Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, 70 Sun Moon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460, Korea.
Molecules. 2019 Jan 10;24(2):244. doi: 10.3390/molecules24020244.
Nargenicin A1 is major secondary metabolite produced by sp. CS682, with an effective antibacterial activity against various Gram-positive bacteria. Most 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.
那尔癸因 A1 是 sp. CS682 产生的主要次生代谢产物，对各种革兰氏阳性菌具有有效的抗菌活性。大多数 spp. 具有产生具有不同性质的化合物的代谢能力，因此可以应用一菌株多产物（OSMAC）方法从这些菌株中获得多样的化合物。在这项研究中，我们通过代谢工程方法对一种新型的 1,3,6,8-四羟基萘（THN）衍生物进行了表征，导致那尔癸因 A1 生物合成的失活。通过基因组挖掘、代谢产物分析和生物信息学，阐明了生物合成基因簇和生物合成机制。此外，还对分离的 THN 化合物的抗菌、抗癌、黑色素形成和 UV 保护特性进行了研究。该化合物没有表现出显著的抗菌和细胞毒性活性，但表现出有希望的 UV 保护作用。因此，代谢工程是发现新型生物活性分子的有效策略。
