Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, California 92093-0204, USA.
J Nat Prod. 2010 Mar 26;73(3):378-82. doi: 10.1021/np900719u.
Organofluorine compounds play an important role in medicinal chemistry, where they are responsible for up to 15% of the pharmaceutical products on the market. While natural products are valuable sources of new chemical entities, natural fluorinated molecules are extremely rare and the pharmaceutical industry has not benefited from a microbial source of this class of compounds. Streptomyces cattleya is an unusual bacterium in that it elaborates fluoroacetate and the amino acid 4-fluorothreonine. The discovery in 2002 of the fluorination enzyme FlA responsible for C-F bond formation in S. cattleya, and its subsequent characterization, opened up for the first time the prospect of genetically engineering fluorometabolite production from fluoride ion in host organisms. As a proof of principle, we report here the induced production of fluorosalinosporamide by replacing the chlorinase gene salL from Salinispora tropica with the fluorinase gene flA.
有机氟化合物在药物化学中起着重要作用，其中约有 15%的上市药物都含有它们。虽然天然产物是新化学实体的宝贵来源，但天然含氟分子极为罕见，制药行业也没有从微生物来源中获得这类化合物。卡特利链霉菌是一种不寻常的细菌，因为它能产生氟乙酸和 4-氟苏氨酸。2002 年发现的氟化酶 FlA 负责卡特利链霉菌中 C-F 键的形成，随后对其进行了表征，这首次为从宿主生物体中的氟离子基因工程化产生氟代谢物开辟了前景。作为原理的证明，我们在这里报告了通过用氟化酶基因 flA 替换海洋放线菌 Salinispora tropica 的叶绿素酶基因 salL 来诱导氟沙利菌素的产生。
