College of Food Science and Technology, Nanjing Agricultural University, 1 Weigang, Nanjing, 210095, China.
College of Food Science and Technology, Nanjing Agricultural University, 1 Weigang, Nanjing, 210095, China.
Biochem Biophys Res Commun. 2021 Feb 12;540:51-55. doi: 10.1016/j.bbrc.2020.12.093. Epub 2021 Jan 12.
Nitrogen heterocycle small molecules display various pharmaceutically important bioactivities and have great potential in drug development and application. Microbes are an important source for discovering nitrogen heterocycle natural products, and the elucidation of their biosynthetic pathways in microbes facilitates genetic manipulation of new nitrogen heterocycle products. In this study, we isolated three isoquinolinequinones from a Streptomyces albus J1074 conjugant and identified their biosynthetic gene cluster in the S. albus J1074 genome. The function of the biosynthetic gene cluster was confirmed by heterologous expression of the gene cluster in S. coelicolor M1146. This study uncovered a new biosynthetic machinery to produce nitrogen heterocycle natural products in microbes.
氮杂环小分子具有各种重要的药物活性，在药物开发和应用方面具有巨大的潜力。微生物是发现氮杂环天然产物的重要来源，阐明微生物中的生物合成途径有助于对新的氮杂环产物进行遗传操作。在本研究中，我们从一株白色链霉菌 J1074 接合子中分离得到三种异喹啉醌，并在白色链霉菌 J1074 基因组中鉴定了它们的生物合成基因簇。通过在变铅青链霉菌 M1146 中异源表达基因簇，证实了该生物合成基因簇的功能。本研究揭示了微生物中产生氮杂环天然产物的新生物合成机制。
