Engineering fluorometabolite production: fluorinase expression in Salinispora tropica Yields Fluorosalinosporamide.
Engineering fluorometabolite production: fluorinase expression in Salinispora tropica Yields Fluorosalinosporamide.
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DOI：
10.1021/np900719u
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发表时间：
2010-03-26
影响因子：
5.1
通讯作者：
Moore, Bradley S.
中科院分区：
文献类型：
--
作者：
Eustaquio, Alessandra S.;O'Hagan, David;Moore, Bradley S.
有机氟化合物在药物化学中发挥着重要作用，占市场上高达 15% 的药品。虽然天然产物是新化学实体的宝贵来源，但天然氟化分子极为罕见，制药行业尚未从此类化合物的微生物来源中受益。卡特兰链霉菌是一种不寻常的细菌，它能产生氟乙酸盐和氨基酸 4-氟苏氨酸。 2002年，在卡特兰中负责C-F键形成的氟化酶FlA的发现及其随后的表征，首次开辟了通过宿主生物体中的氟离子进行基因工程生产含氟代谢物的前景。作为原理证明，我们在这里报告了通过用氟酶基因 flA 替换来自热带盐孢菌的氯酶基因 salL 来诱导产生氟盐孢酰胺。
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.
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影响因子：
18.3
作者：
Blasiak, Leah C.;Drennan, Catherine L.
通讯作者：
Drennan, Catherine L.
DOI：
10.1073/pnas.0700962104
发表时间：
2007-06-19
影响因子：
11.1
作者：
Udwary, Daniel W.;Zeigler, Lisa;Moore, Bradley S.
通讯作者：
Moore, Bradley S.
影响因子：
5.1
作者：
Reed, Katherine A.;Manam, Rama Rao;Potts, Barbara C. M.
通讯作者：
Potts, Barbara C. M.
影响因子：
1.9
作者：
ZININ, VN;ILYASOV, AV;THIELE, H
通讯作者：
THIELE, H
影响因子：
--
作者：
Huang, Fanglu;Haydock, Stephen F.;Spencer, Jonathan B.
通讯作者：
Spencer, Jonathan B.