Biotechnology Research Center, The University of Tokyo, 1-1-1 Yayoi, Tokyo 113-8657, Japan.
Bioorg Med Chem Lett. 2012 Sep 15;22(18):5823-6. doi: 10.1016/j.bmcl.2012.07.084. Epub 2012 Jul 31.
Furaquinocin is a natural polyketide-isoprenoid hybrid (meroterpenoid) produced by Streptomyces sp. strain KO-3988. All of the fur genes required for furaquinocin biosynthesis have been cloned, and the heterologous production of furaquinocin has been demonstrated in Streptomyces albus. Here, we report the identification of 8-amino-2,5,7-trihydroxynaphthalene-1,4-dione (8-amino-flaviolin) produced by the S. albus heterologous expression of the three contiguous genes encoding type III polyketide synthase (Fur1), monooxygenase (Fur2), and aminotransferase (Fur3) in the furaquinocin biosynthetic gene cluster. An S. albus transformant (S. albus/pWHM-Fur2_del3) harboring the fur gene cluster and lacking the fur3 gene did not produce furaquinocin, whereas furaquinocin production was restored when 8-amino-flaviolin was added to the culture medium of S. albus/pWHM-Fur2_del3. These results demonstrate that Fur3 aminotransferase is essential for furaquinocin biosynthesis and that 8-amino-flaviolin is an early-stage intermediate in furaquinocin biosynthesis. We propose that the biosynthetic pathway generating 8-amino-flaviolin is the common route for the biosynthesis of Streptomyces meroterpenoids.
呋喃喹啉酮是一种天然聚酮-异戊二烯杂合（杂萜）化合物，由链霉菌 KO-3988 产生。呋喃喹啉酮生物合成所需的所有呋喃基因都已被克隆，并且在白色链霉菌中已经证明了呋喃喹啉酮的异源生产。在这里，我们报告了由编码 III 型聚酮合酶（Fur1）、单加氧酶（Fur2）和氨基转移酶（Fur3）的三个连续基因在呋喃喹啉酮生物合成基因簇中的白色链霉菌异源表达所产生的 8-氨基-2,5,7-三羟基萘-1,4-二酮（8-氨基黄酮醇）的鉴定。含有呋喃基因簇但缺乏 fur3 基因的白色链霉菌转化体（S. albus/pWHM-Fur2_del3）没有产生呋喃喹啉酮，而当 8-氨基黄酮醇添加到 S. albus/pWHM-Fur2_del3 的培养基中时，呋喃喹啉酮的生产得以恢复。这些结果表明 Fur3 氨基转移酶是呋喃喹啉酮生物合成所必需的，并且 8-氨基黄酮醇是呋喃喹啉酮生物合成的早期中间体。我们提出，生成 8-氨基黄酮醇的生物合成途径是生成 Streptomyces 杂萜的共同途径。
